Cited by 317Hemoglobin structure and functionHemoglobinopathies and Related DisordersProtein Interaction Studies and Fluorescence Analysis

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Hemoglobin: Structure, Function and Allostery

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Ahmed, Mostafa H., Ghatge, Mohini S., Safo, Martin K.·2020·Subcellular Biochemistry

DOI 10.1007/978-3-030-41769-7_14PMC PMC7370311

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Abstract

This chapter reviews how allosteric (heterotrophic) effectors and natural mutations impact hemoglobin (Hb) primary physiological function of oxygen binding and transport. First, an introduction about the structure of Hb is provided, including the ensemble of tense and relaxed Hb states and the dynamic equilibrium of Hb multistate. This is followed by a brief review of Hb variants with altered Hb structure and oxygen binding properties. Finally, a review of different endogenous and exogenous allosteric effectors of Hb is presented with particular emphasis on the atomic interactions of synthetic ligands with altered allosteric function of Hb that could potentially be harnessed for the treatment of diseases.

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Pathogenesis and Treatment of Sickle Cell Disease
Bunn, H. F. (1997) · New England Journal of Medicine · doi:10.1056/nejm199709113371107 · Cited by 1,154 · cited 2×
“…HbS molecule binds to a hydrophobic pocket on an adjacent deoxygenated HbS molecule, joining the molecules together to form insoluble polymers and giving rise to the classical sickle red blood cell (RBC) morphology (Eaton and Hofrichter 1990; Bunn 1997; Harrington et al. Subcell Biochem.”
Background
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Thom, C. S., Dickson, C. F., Gell, D. A., & Weiss, M. J. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011858 · Cited by 336
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Metcalf, B., Chuang, C., Dufu, K., Patel, M. P., Silva-Garcia, A., Johnson, C., Lu, Q., Partridge, J. R., Patskovska, L., Patskovsky, Y., et al. (2017) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6b00491 · Cited by 203
Structure-Function Relations of Human Hemoglobins
Marengo-Rowe, A. J. (2006) · Baylor University Medical Center Proceedings · doi:10.1080/08998280.2006.11928171 · Cited by 179

Show all 4 references

Research works printed but not linked: 195

Abdulmalik O, Safo MK, Lerner NB et al (2004) Characterization of hemoglobin bassett (alpha94Asp → Ala), a variant with very low oxygen affinity. Am J Hematol 77:268–276. https://doi.org/10.1002/ajh.20184 · DOI
Abdulmalik O, Safo MK, Chen Q et al (2005) 5-hydroxymethyl-2-furfural modifies intracellular sickle haemoglobin and inhibits sickling of red blood cells. Br J Haematol 128:552–561. https://doi.org/10.1111/j.1365-2141.2004.05332.x · DOI
Abdulmalik O, Ghatge MS, Musayev FN et al (2011) Crystallographic analysis of human hemoglobin elucidates the structural basis of the potent and dual antisickling activity of pyridyl derivatives of vanillin Corrigendum. Acta Crystallogr D Biol Crystallogr 67:1076. https://doi.org/10.1107/S0907444911045860 · DOI
Abraham DJ, Mehanna AS, Williams FL (1982) Design, synthesis, and testing of potential antisickling agents. 1. halogenated benzyloxy and phenoxy acids. J Med Chem 25:1015–1017. https://doi.org/10.1021/jm00351a002 · DOI
Abraham DJ, Perutz MF, Phillips SE (1983a) Physiological and x-ray studies of potential antisickling agents. Proc Natl Acad Sci USA 80:324–328. https://doi.org/10.1073/pnas.80.2.324 · DOI
Abraham DJ, Perutz MF, Phillips SE (1983b) Physiological and x-ray studies of potential antisickling agents. PNAS 80:324–328. https://doi.org/10.1073/pnas.80.2.324 · DOI
Abraham DJ, Kennedy PE, Mehanna AS et al (1984) Design, synthesis, and testing of potential antisickling agents. 4. structure-activity relationships of benzyloxy and phenoxy acids. J Med Chem 27:967–978. https://doi.org/10.1021/jm00374a006 · DOI
Abraham DJ, Mehanna AS, Wireko FC et al (1991) Vanillin, a potential agent for the treatment of sickle cell anemia. Blood 77:1334–1341 · DOI
Abraham DJ, Peascoe RA, Randad RS, Panikker J (1992a) X-ray diffraction study of di and tetra-ligated T-state hemoglobin from high salt crystals. J Mol Biol 227:480–492. https://doi.org/10.1016/0022-2836(92)90902-V · DOI
Abraham DJ, Wireko FC, Randad RS et al (1992b) Allosteric modifiers of hemoglobin: 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl]phenoxy]-2-methylpropionic acid derivatives that lower the oxygen affinity of hemoglobin in red cell suspensions, in whole blood, and in vivo in rats. Biochemistry 31:9141–9149. https://doi.org/10.1021/bi00153a005 · DOI
Abraham DJ, Safo MK, Boyiri T et al (1995) How allosteric effectors can bind to the same protein residue and produce opposite shifts in the allosteric equilibrium. Biochemistry 34:15006–15020. https://doi.org/10.1021/bi00046a007 · DOI
Akinsheye I, Klings ES (2010) Sickle cell anemia and vascular dysfunction: the nitric oxide connection. J Cell Physiol 224:620–625. https://doi.org/10.1002/jcp.22195 · DOI
Aliyu ZY, Gordeuk V, Sachdev V et al (2008) Prevalence and risk factors for pulmonary artery systolic hypertension among sickle cell disease patients in Nigeria. Am J Hematol 83:485–490. https://doi.org/10.1002/ajh.21162 · DOI
Arnone A (1972) X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhaemoglobin. Nature 237:146–149. https://doi.org/10.1038/237146a0 · DOI
Arous N, Braconnier F, Thillet J et al (1981) Hemoglobin Saint Mandé beta 102 (G4) asn replaced by tyr: a new low oxygen affinity variant. FEBS Lett 126:114–116. https://doi.org/10.1016/0014-5793(81)81046-0 · DOI
Baldwin J, Chothia C (1979) Haemoglobin: The structural changes related to ligand binding and its allosteric mechanism. J Mol Biol 129:175–220. https://doi.org/10.1016/0022-2836(79)90277-8 · DOI
Barrick D, Ho NT, Simplaceanu V et al (1997) A test of the role of the proximal histidines in the Perutz model for cooperativity in haemoglobin. Nat Struct Biol 4:78–83 · DOI
Beddell CR, Goodford PJ, Kneen G et al (1984) Substituted benzaldehydes designed to increase the oxygen affinity of human haemoglobin and inhibit the sickling of sickle erythrocytes. Br J Pharmacol 82:397–407. https://doi.org/10.1111/j.1476-5381.1984.tb10775.x · DOI
Belcher JD, Bryant CJ, Nguyen J et al (2003) Transgenic sickle mice have vascular inflammation. Blood 101:3953–3959. https://doi.org/10.1182/blood-2002-10-3313 · DOI
Benesch R, Benesch RE (1967) The effect of organic phosphates from the human erythrocyte on the allosteric properties of hemoglobin. Biochem Biophys Res Commun 26:162–167. https://doi.org/10.1016/0006-291X(67)90228-8 · DOI
Benesch RE, Kwong S, Edalji R, Benesch R (1979) Alpha chain mutations with opposite effects on the gelation of hemoglobin S. J Biol Chem 254:8169–8172 · DOI
Berenbrink M (2006) Evolution of vertebrate haemoglobins: Histidine side chains, specific buffer value and Bohr effect. Respir Physiol Neurobiol 154:165–184. https://doi.org/10.1016/j.resp.2006.01.002 · DOI
Bettati S, Mozzarelli A (1997) T state hemoglobin binds oxygen noncooperatively with allosteric effects of protons, inositol hexaphosphate, and chloride. J Biol Chem 272:32050–32055. https://doi.org/10.1074/jbc.272.51.32050 · DOI
Bettati S, Mozzarelli A, Perutz MF (1998) Allosteric mechanism of haemoglobin: rupture of salt-bridges raises the oxygen affinity of the T-structure. J Mol Biol 281:581–585. https://doi.org/10.1006/jmbi.1998.1983 · DOI
Biolo A, Greferath R, Siwik DA et al (2009) Enhanced exercise capacity in mice with severe heart failure treated with an allosteric effector of hemoglobin, myo-inositol trispyrophosphate. PNAS 106:1926–1929. https://doi.org/10.1073/pnas.0812381106 · DOI
Birukou I, Soman J, Olson JS (2011) Blocking the gate to ligand entry in human hemoglobin. J Biol Chem 286:10515–10529. https://doi.org/10.1074/jbc.M110.176271 · DOI
Bissé E, Schaeffer-Reiss C, Van Dorsselaer A et al (2017) Hemoglobin Kirklareli (α H58L), a new variant associated with iron deficiency and increased CO binding. J Biol Chem 292:2542–2555. https://doi.org/10.1074/jbc.M116.764274 · DOI
Bohr C, Hasselbalch K, Krogh A (1904) Ueber einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensäurespannung des Blutes auf dessen Sauerstoffbindung übt1. Skandinavisches Archiv Für Physiologie 16:402–412. https://doi.org/10.1111/j.1748-1716.1904.tb01382.x · DOI
Bonaventura J, Riggs A (1968) Hemoglobin Kansas, a human hemoglobin with a neutral amino acid substitution and an abnormal oxygen equilibrium. J Biol Chem 243:980–991 · DOI
Bonaventura C, Arumugam M, Cashon R et al (1994) Chloride masks effects of opposing positive charges in Hb A and Hb Hinsdale (β139 Asn → Lys) that can modulate cooperativity as well as oxygen affinity. J Mol Biol 239:561–568. https://doi.org/10.1006/jmbi.1994.1395 · DOI
Borg I, Valentino M, Fiorini A, Felice AE (1997) Hb Setif [alpha 94(G1)Asp → Tyr] in Malta. Hemoglobin 21:91–96 · DOI
Botha MC, Beale D, Isaacs WA, Lehmann H (1966) Hemoglobin J Cape Town-alpha-2 92 arginine replaced by glutamine beta-2. Nature 212:792–795. https://doi.org/10.1038/212792a0 · DOI
Boyiri T, Safo MK, Danso-Danquah RE et al (1995) Bisaldehyde allosteric effectors as molecular ratchets and probes. Biochemistry 34:15021–15036. https://doi.org/10.1021/bi00046a008 · DOI
Brunori M, Coletta M, Di Cera E (1986) A cooperative model for ligand binding to biological macromolecules as applied to oxygen carriers. Biophys Chem 23:215–222. https://doi.org/10.1016/0301-4622(86)85006-2 · DOI
Bunn HF, Bradley TB, Davis WE et al (1972) Structural and functional studies on hemoglobin Bethesda (alpha2beta2 145His), a varient associated with compensatory erythrocytosis. J Clin Invest 51:2299–2309. https://doi.org/10.1172/JCI107040 · DOI
Busch MR, Ho C (1990) Effects of anions on the molecular basis of the Bohr effect of hemoglobin. Biophys Chem 37:313–322. https://doi.org/10.1016/0301-4622(90)88031-M · DOI
Carrell RW, Lehmann H, Hutchison HE (1966) Haemoglobin Köln (beta-98 valine–methionine): an unstable protein causing inclusion-body anaemia. Nature 210:915–916. https://doi.org/10.1038/210915a0 · DOI
Charache S, Weatherall DJ, Clegg JB (1966) Polycythemia associated with a hemoglobinopathy. J Clin Invest 45:813–822. https://doi.org/10.1172/JCI105397 · DOI
Chen Q, Lalezari I, Nagel RL, Hirsch RE (2005) Liganded hemoglobin structural perturbations by the allosteric effector L35. Biophys J 88:2057–2067. https://doi.org/10.1529/biophysj.104.046136 · DOI
Como PF, Wylie BR, Trent RJ et al (1991) A new unstable and low oxygen affinity hemoglobin variant: Hb Stanmore [beta 111(G13)Val–Ala]. Hemoglobin 15:53–65 · DOI
Connor J, Pak CC, Schroit AJ (1994) Exposure of phosphatidylserine in the outer leaflet of human red blood cells. relationship to cell density, cell age, and clearance by mononuclear cells. J Biol Chem 269:2399–2404 · DOI
Czerminski R, Elber R (1991) Computational studies of ligand diffusion in globins: I. Leghemoglobin. Proteins: Struct Funct Bioinform 10:70–80. https://doi.org/10.1002/prot.340100107 · DOI
Dacie JV, Shinton NK, Gaffney PJ, Lehmann H (1967) Haemoglobin Hammersmith (beta-42 (CDI) Phe replaced by ser). Nature 216:663–665. https://doi.org/10.1038/216663a0 · DOI
De Franceschi L (2009) Pathophisiology of sickle cell disease and new drugs for the treatment. Mediterr J Hematol Infect Dis 1:e2009024. https://doi.org/10.4084/MJHID.2009.024 · DOI
Deshpande TM, Pagare PP, Ghatge MS et al (2018) Rational modification of vanillin derivatives to stereospecifically destabilize sickle hemoglobin polymer formation. Acta Crystallogr D Struct Biol 74:956–964. https://doi.org/10.1107/S2059798318009919 · DOI
Dinçol G, Dinçol K, Erdem S et al (1994) Hb Capa or alpha (2)94(G1)Asp → Gly beta 2, a mildly unstable variant with an A → G (GAC → GGC) mutation in codon 94 of the alpha 1-globin gene. Hemoglobin 18:57–60 · DOI
Doyle ML, Lew G, Turner GJ et al (1992) Regulation of oxygen affinity by quaternary enhancement: does hemoglobin ypsilanti represent an allosteric intermediate? Proteins: Struct Funct Bioinform 14:351–362. https://doi.org/10.1002/prot.340140304 · DOI
Eaton WA, Hofrichter J (1990) Sickle cell hemoglobin polymerization. Adv Protein Chem 40:63–279 · DOI
Efremov GD, Stojmirovic E, Lam HL et al (1978) HB Beth Israel (beta 102 [G4] Asn replaced by Ser) observed in a Yugoslavian teenager. Hemoglobin 2:75–77. https://doi.org/10.3109/03630267808999192 · DOI
Elber R (2010) Ligand diffusion in globins: simulations versus experiment. Curr Opin Struct Biol 20:162–167. https://doi.org/10.1016/j.sbi.2010.01.002 · DOI
Fan J-S, Zheng Y, Choy W-Y et al (2013) Solution structure and dynamics of human hemoglobin in the carbonmonoxy form. Biochemistry 52:5809–5820. https://doi.org/10.1021/bi4005683 · DOI
Fermi G (1975) Three-dimensional fourier synthesis of human deoxyhaemoglobin at 2–5 a resolution: refinement of the atomic model. J Mol Biol 97:237–256. https://doi.org/10.1016/s0022-2836(75)80037-4 · DOI
Fernandez EJ, Abad-Zapatero C, Olsen KW (2000) Crystal structure of Lysβ182-Lysβ282 crosslinked hemoglobin: A possible allosteric intermediate 11 Edited by K. Nagai. J Mol Biol 296:1245–1256. https://doi.org/10.1006/jmbi.2000.3525 · DOI
Fronticelli C, Pechik I, Brinigar WS et al (1994) Chloride ion independence of the Bohr effect in a mutant human hemoglobin beta (V1M + H2deleted). J Biol Chem 269:23965–23969 · DOI
Gell DA (2018) Structure and function of haemoglobins. Blood Cells Mol Dis 70:13–42. https://doi.org/10.1016/j.bcmd.2017.10.006 · DOI
Ghatge MS, Ahmed MH, Omar ASM et al (2016) Crystal structure of carbonmonoxy sickle hemoglobin in R-state conformation. J Struct Biol 194:446–450. https://doi.org/10.1016/j.jsb.2016.04.003 · DOI
Goldstein SR, Liu C, Safo MK et al (2018) Design, synthesis, and biological evaluation of allosteric effectors that enhance CO release from carboxyhemoglobin. ACS Med Chem Lett 9:714–718. https://doi.org/10.1021/acsmedchemlett.8b00166 · DOI
Gong Q, Simplaceanu V, Lukin JA et al (2006) Quaternary structure of carbonmonoxyhemoglobins in solution: structural changes induced by the allosteric effector inositol hexaphosphate. Biochemistry 45:5140–5148. https://doi.org/10.1021/bi052424h · DOI
Grasso JA, Sullivan AL, Sullivan LW (1975) Ultrastructural studies of the bone marrow in sickle cell anaemia. II. the morphology of erythropoietic cells and their response to deoxygenation in vitro. Br J Haematol 31:381–389. https://doi.org/10.1111/j.1365-2141.1975.tb00869.x · DOI
Gupta RK, Benovic JL, Rose ZB (1979) Location of the allosteric site for 2,3-bisphosphoglycerate on human oxy- and deoxyhemoglobin as observed by magnetic resonance spectroscopy. J Biol Chem 254:8250–8255 · DOI
Hänel P, Andréani P, Gräler MH (2007) Erythrocytes store and release sphingosine 1-phosphate in blood. FASEB J 21:1202–1209. https://doi.org/10.1096/fj.06-7433com · DOI
Hardison R, Chao KM, Schwartz S et al (1994) Globin gene server: a prototype E-mail database server featuring extensive multiple alignments and data compilation for electronic genetic analysis. Genomics 21:344–353. https://doi.org/10.1006/geno.1994.1275 · DOI
Hardison RC, Chui DH, Riemer C et al (2001) Databases of human hemoglobin variants and other resources at the globin gene server. Hemoglobin 25:183–193 · DOI
Harrington DJ, Adachi K, Royer WE (1997) The high resolution crystal structure of deoxyhemoglobin S. J Mol Biol 272:398–407. https://doi.org/10.1006/jmbi.1997.1253 · DOI
He Z, Russell JE (2004a) Effect of zeta-globin substitution on the O2-transport properties of Hb S in vitro and in vivo. Biochem Biophys Res Commun 325:1376–1382. https://doi.org/10.1016/j.bbrc.2004.10.180 · DOI
He Z, Russell JE (2004b) Antisickling effects of an endogenous human alpha-like globin. Nat Med 10:365–367. https://doi.org/10.1038/nm1022 · DOI
Henry ER, Bettati S, Hofrichter J, Eaton WA (2002) A tertiary two-state allosteric model for hemoglobin. Biophys Chem 98:149–164. https://doi.org/10.1016/S0301-4622(02)00091-1 · DOI
Huisman THJ, Carver MFH, Efremov G (1996) A syllabus of human hemoglobin variants. The Sickle Cell Anemia Foundation, Augusta, GA, USA
Ito K, Anada Y, Tani M et al (2007) Lack of sphingosine 1-phosphate-degrading enzymes in erythrocytes. Biochem Biophys Res Commun 357:212–217. https://doi.org/10.1016/j.bbrc.2007.03.123 · DOI
Janin J, Wodak SJ (1993) The quaternary structure of carbonmonoxy hemoglobin ypsilanti. Proteins: Struct Funct Bioinform 15:1–4. https://doi.org/10.1002/prot.340150102 · DOI
Jayaraman V, Rodgers KR, Mukerji I, Spiro TG (1995) Hemoglobin allostery: resonance Raman spectroscopy of kinetic intermediates. Science 269:1843–1848. https://doi.org/10.1126/science.7569921 · DOI
Jenkins JD, Musayev FN, Danso-Danquah R et al (2009) Structure of relaxed-state human hemoglobin: insight into ligand uptake, transport and release. Acta Cryst D 65:41–48. https://doi.org/10.1107/S0907444908037256 · DOI
Jensen M, Oski FA, Nathan DG, Bunn HF (1975) Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. observations on the auto-oxidation of normal and variant hemoglobins. J Clin Invest 55:469–477. https://doi.org/10.1172/JCI107953 · DOI
Jones RT, Osgood EE, Brimhall B, Koler RD (1967) Hemoglobin Yakina. I. clinical and biochemical studies. J Clin Invest 46:1840–1847. https://doi.org/10.1172/JCI105674 · DOI
Jorge SE, Bringas M, Petruk AA et al (2018) Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra. Arch Biochem Biophys 637:73–78. https://doi.org/10.1016/j.abb.2017.11.010 · DOI
Kamel K, el-Najjar A, Webber BB et al (1985) Hb Doha or alpha 2 beta 2[X-N-Met-1(NA1)Val–Glu]; a new beta-chain abnormal hemoglobin observed in a Qatari female. Biochim Biophys Acta 831:257–260. https://doi.org/10.1016/0167-4838(85)90043-3 · DOI
Kato GJ, Lawrence MP, Mendelsohn LG et al (2013) Phase 1 clinical trial of the candidate anti-sickling agent Aes-103 In adults with sickle cell anemia. Blood 122:1009–1009 · DOI
Kavanaugh JS, Rogers PH, Case DA, Arnone A (1992) High-resolution x-ray study of deoxyhemoglobin Rothschild 37.beta. Trp.fwdarw. Arg: a mutation that creates an intersubunit chloride-binding site. Biochemistry 31:4111–4121. https://doi.org/10.1021/bi00131a030 · DOI
Kavanaugh JS, Weydert JA, Rogers PH et al (2001) Site-directed mutations of human hemoglobin at residue 35beta: a residue at the intersection of the alpha1beta1, alpha1beta2, and alpha1alpha2 interfaces. Protein Sci 10:1847–1855. https://doi.org/10.1110/ps.16401 · DOI
Kavanaugh JS, Rogers PH, Arnone A (2005) Crystallographic evidence for a new ensemble of ligand-induced allosteric transitions in hemoglobin: the T-to-T(high) quaternary transitions. Biochemistry 44:6101–6121. https://doi.org/10.1021/bi047813a · DOI
Khandelwal SR, Randad RS, Lin PS et al (1993) Enhanced oxygenation in vivo by allosteric inhibitors of hemoglobin saturation. Am J Physiol 265:H1450–H1453. https://doi.org/10.1152/ajpheart.1993.265.4.H1450 · DOI
Kilmartin JV, Imai K, Jones RT et al (1978) Role of Bohr group salt bridges in cooperativity in hemoglobin. Biochim Biophys Acta 534:15–25. https://doi.org/10.1016/0005-2795(78)90471-3 · DOI
King MA, Wiltshire BG, Lehmann H, Morimoto H (1972) An unstable haemoglobin with reduced oxygen affinity: haemoglobin Peterborough, 3 (GI3) Valine lead to Phenylalanine, its interaction with normal haemoglobin and with haemoglobin Lepore. Br J Haematol 22:125–134. https://doi.org/10.1111/j.1365-2141.1972.tb08794.x · DOI
Kister J, Kiger L, Francina A et al (1995) Hemoglobin Roanne [alpha 94(G1) Asp → Glu]: a variant of the alpha 1 beta 2 interface with an unexpected high oxygen affinity. Biochim Biophys Acta 1246:34–38. https://doi.org/10.1016/0167-4838(94)00190-r · DOI
Kleinberg L, Grossman SA, Piantadosi S et al (1999) Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme. J Clin Oncol 17:2593–2603. https://doi.org/10.1200/JCO.1999.17.8.2593 · DOI
Koshland DE, Némethy G, Filmer D (1966) Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5:365–385. https://doi.org/10.1021/bi00865a047 · DOI
Kosmachevskaya OV, Topunov AF (2018) Alternate and additional functions of erythrocyte hemoglobin. Biochem Mosc 83:1575–1593. https://doi.org/10.1134/S0006297918120155 · DOI
Laberge M, Kövesi I, Yonetani T, Fidy J (2005) R-state hemoglobin bound to heterotropic effectors: models of the DPG, IHP and RSR13 binding sites. FEBS Lett 579:627–632. https://doi.org/10.1016/j.febslet.2004.12.033 · DOI
Ladner RC, Heidner EJ, Perutz MF (1977) The structure of horse methaemoglobin at 2-0 A resolution. J Mol Biol 114:385–414. https://doi.org/10.1016/0022-2836(77)90256-x · DOI
Lalezari I, Rahbar S, Lalezari P et al (1988) LR16, a compound with potent effects on the oxygen affinity of hemoglobin, on blood cholesterol, and on low density lipoprotein. PNAS 85:6117–6121. https://doi.org/10.1073/pnas.85.16.6117 · DOI
Lalezari I, Lalezari P, Poyart C et al (1990) New effectors of human hemoglobin: structure and function. Biochemistry 29:1515–1523. https://doi.org/10.1021/bi00458a024 · DOI
Lokich JJ, Moloney WC, Bunn HF et al (1973) Hemoglobin brigham (alpha2Abeta2100 Pro–Leu). Hemoglobin variant associated with familial erythrocytosis. J Clin Invest 52:2060–2067. https://doi.org/10.1172/JCI107390 · DOI
Lukin JA, Ho C (2004) The structure–function relationship of hemoglobin in solution at atomic resolution. Chem Rev 104:1219–1230. https://doi.org/10.1021/cr940325w · DOI
Lukin JA, Kontaxis G, Simplaceanu V et al (2003) Quaternary structure of hemoglobin in solution. PNAS 100:517–520. https://doi.org/10.1073/pnas.232715799 · DOI
Lukin JA, Kontaxis G, Simplaceanu V et al (2004) Backbone resonance assignments of human adult hemoglobin in the carbonmonoxy form. J Biomol NMR 28:203–204. https://doi.org/10.1023/B:JNMR.0000013816.64039.6f · DOI
Mairbäurl H, Weber RE (2012) Oxygen transport by hemoglobin. Compr Physiol 2:1463–1489. https://doi.org/10.1002/cphy.c080113 · DOI
Makowski L, Bardhan J, Gore D et al (2011) WAXS studies of the structural diversity of hemoglobin in solution. J Mol Biol 408:909–921. https://doi.org/10.1016/j.jmb.2011.02.062 · DOI
Marden MC, Bohn B, Kister J, Poyart C (1990) Effectors of hemoglobin. separation of allosteric and affinity factors. Biophys J 57:397–403. https://doi.org/10.1016/S0006-3495(90)82556-X · DOI
Mehanna AS, Abraham DJ (1990) Comparison of crystal and solution hemoglobin binding of selected antigelling agents and allosteric modifiers. Biochemistry 29:3944–3952. https://doi.org/10.1021/bi00468a022 · DOI
Monod J, Wyman J, Changeux JP (1965) On the nature of allosteric transitions: a plausible model. J Mol Biol 12:88–118. https://doi.org/10.1016/s0022-2836(65)80285-6 · DOI
Mozzarelli A, Rivetti C, Rossi GL et al (1991) Crystals of haemoglobin with the T quaternary structure bind oxygen noncooperatively with no Bohr effect. Nature 351:416–419. https://doi.org/10.1038/351416a0 · DOI
Mueser TC, Rogers PH, Arnone A (2000) Interface sliding as illustrated by the multiple quaternary structures of liganded hemoglobin. Biochemistry 39:15353–15364. https://doi.org/10.1021/bi0012944 · DOI
Muirhead H, Perutz MF (1963) Structure of hæemoglobin: a three-dimensional Fourier synthesis of reduced human haemoglobin at 5.5 Å resolution. Nature 199:633–638. https://doi.org/10.1038/199633a0 · DOI
Murari J, Smith LL, Wilson JB et al (1977) Some properties of hemoglobin Gun Hill. Hemoglobin 1:267–282 · DOI
Nagel RL, Johnson J, Bookchin RM et al (1980) Beta-chain contact sites in the haemoglobin S polymer. Nature 283:832–834. https://doi.org/10.1038/283832a0 · DOI
Nakagawa A, Lui FE, Wassaf D et al (2014) Identification of a small molecule that increases hemoglobin oxygen affinity and reduces SS erythrocyte sickling. ACS Chem Biol 9:2318–2325. https://doi.org/10.1021/cb500230b · DOI
Nakagawa A, Ferrari M, Schleifer G et al (2018) A triazole disulfide compound increases the affinity of hemoglobin for oxygen and reduces the sickling of human sickle cells. Mol Pharm 15:1954–1963. https://doi.org/10.1021/acs.molpharmaceut.8b00108 · DOI
Nienhuis AW (1987) Hemoglobin: Molecular, genetic and clinical aspects: By H. F. Bunn and B. G. Forget. Philadelphia: W. B. Saunders Company. (1986). 690 pp. $99.00. Cell 48:731. https://doi.org/10.1016/0092-8674(87)90069-9 · DOI
Nnamani IN, Joshi GS, Danso-Danquah R et al (2008) Pyridyl derivatives of benzaldehyde as potential antisickling agents. Chem Biodivers 5:1762–1769. https://doi.org/10.1002/cbdv.200890165 · DOI
Noble RW, Hui HL, Kwiatkowski LD et al (2001) Mutational effects at the subunit interfaces of human hemoglobin: evidence for a unique sensitivity of the T quaternary state to changes in the hinge region of the alpha 1 beta 2 interface. Biochemistry 40:12357–12368. https://doi.org/10.1021/bi010988p · DOI
O’Donnell S, Mandaro R, Schuster TM, Arnone A (1979) X-ray diffraction and solution studies of specifically carbamylated human hemoglobin A. evidence for the location of a proton- and oxygen-linked chloride binding site at valine 1 alpha. J Biol Chem 254:12204–12208 · DOI
Oksenberg D, Dufu K, Patel MP et al (2016) GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease. Br J Haematol 175:141–153. https://doi.org/10.1111/bjh.14214 · DOI
Omar AM, Mahran MA, Ghatge MS et al (2015) Identification of a novel class of covalent modifiers of hemoglobin as potential antisickling agents. Org Biomol Chem 13:6353–6370. https://doi.org/10.1039/c5ob00367a · DOI
Omar AM, Mahran MA, Ghatge MS et al (2016) Aryloxyalkanoic acids as non-covalent modifiers of the allosteric properties of hemoglobin. Molecules 21. https://doi.org/10.3390/molecules21081057 · DOI
Pagare PP, Ghatge MS, Musayev FN et al (2018) Rational design of pyridyl derivatives of vanillin for the treatment of sickle cell disease. Bioorg Med Chem 26:2530–2538. https://doi.org/10.1016/j.bmc.2018.04.015 · DOI
Pagel PS, Hettrick DA, Montgomery MW et al (1998) RSR13, a synthetic allosteric modifier of hemoglobin, enhances recovery of stunned myocardium in dogs. Adv Exp Med Biol 454:527–531. https://doi.org/10.1007/978-1-4615-4863-8_63 · DOI
Paoli M, Liddington R, Tame J et al (1996) Crystal structure of T state haemoglobin with oxygen bound at all four haems. J Mol Biol 256:775–792. https://doi.org/10.1006/jmbi.1996.0124 · DOI
Patwa DC, Abraham DJ, Hung TC (1987) Design, synthesis, and testing of potential antisickling agents. 6. Rheologic studies with active phenoxy and benzyloxy acids. Blood Cells 12:589–601
Perrella M, Cera ED (1999) CO ligation intermediates and the mechanism of hemoglobin cooperativity. J Biol Chem 274:2605–2608. https://doi.org/10.1074/jbc.274.5.2605 · DOI
Perutz MF (1972a) Stereochemical mechanism of cooperative effects in haemoglobin. Biochimie 54:587–588. https://doi.org/10.1016/s0300-9084(72)80142-1 · DOI
Perutz MF (1972b) Nature of haem-haem interaction. Nature 237:495–499. https://doi.org/10.1038/237495a0 · DOI
Perutz MF (1976) Structure and mechanism of haemoglobin. Br Med Bull 32:195–208. https://doi.org/10.1093/oxfordjournals.bmb.a071363 · DOI
Perutz MF (1983) Species adaptation in a protein molecule. Mol Biol Evol 1:1–28. https://doi.org/10.1093/oxfordjournals.molbev.a040299 · DOI
Perutz MF (1989) Myoglobin and haemoglobin: role of distal residues in reactions with haem ligands. Trends Biochem Sci 14:42–44. https://doi.org/10.1016/0968-0004(89)90039-X · DOI
Perutz MF, Poyart C (1983) Bezafibrate lowers oxygen affinity of haemoglobin. The Lancet 322:881–882. https://doi.org/10.1016/S0140-6736(83)90870-X · DOI
Perutz MF, Muirhead H, Cox JM, Goaman LC (1968) Three-dimensional Fourier synthesis of horse oxyhaemoglobin at 2.8 A resolution: the atomic model. Nature 219:131–139. https://doi.org/10.1038/219131a0 · DOI
Perutz MF, Muirhead H, Mazzarella L et al (1969) Identification of residues responsible for the alkaline Bohr effect in haemoglobin. Nature 222:1240–1243. https://doi.org/10.1038/2221240a0 · DOI
Perutz MF, Giulio Fermi, Abraham DJ et al (1986) Hemoglobin as a receptor of drugs and peptides: x-ray studies of the stereochemistry of binding. J Am Chem Soc 108:1064–1078. https://doi.org/10.1021/ja00265a036 · DOI
Perutz MF, Fermi G, Poyart C et al (1993) A novel allosteric mechanism in haemoglobin: structure of bovine deoxyhaemoglobin, absence of specific chloride-binding sites and origin of the chloride-linked Bohr effect in bovine and human haemoglobin. J Mol Biol 233:536–545. https://doi.org/10.1006/jmbi.1993.1530 · DOI
Perutz MF, Shih DT -b., Williamson D (1994) The chloride effect in human haemoglobin. a new kind of allosteric mechanism. J Mol Biol 239:555–560. https://doi.org/10.1006/jmbi.1994.1394 · DOI
Perutz MF, Wilkinson AJ, Paoli M, Dodson GG (1998) The stereochemical mechanism of the cooperative effects in hemoglobin revisited. Annu Rev Biophys Biomol Struct 27:1–34. https://doi.org/10.1146/annurev.biophys.27.1.1 · DOI
Phelps Grella M, Danso-Danquah R, Safo MK et al (2000) Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin. J Med Chem 43:4726–4737. https://doi.org/10.1021/jm000199q · DOI
Plaseska D, Dimovski AJ, Wilson JB et al (1991) Hemoglobin Montreal: a new variant with an extended beta chain due to a deletion of Asp, Gly, Leu at positions 73, 74, and 75, and an insertion of Ala, Arg, Cys, Gln at the same location. Blood 77:178–181 · DOI
Poillon WN, Kim BC, Welty EV, Walder JA (1986) The effect of 2,3-diphosphoglycerate on the solubility of deoxyhemoglobin S. Arch Biochem Biophys 249:301–305. https://doi.org/10.1016/0003-9861(86)90006-8 · DOI
Randad RS, Mahran MA, Mehanna AS, Abraham DJ (1991) Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents. J Med Chem 34:752–757. https://doi.org/10.1021/jm00106a041 · DOI
Reissmann KR, Ruth WE, Nomura T (1961) A human hemoglobin with lowered oxygen affinity and impaired heme-heme interactions. J Clin Invest 40:1826–1833. https://doi.org/10.1172/JCI104406 · DOI
Rhoda MD, Martin J, Blouquit Y et al (1983) Sickle cell hemoglobin fiber formation strongly inhibited by the Stanleyville II mutation (alpha 78 Asn leads to Lys). Biochem Biophys Res Commun 111:8–13. https://doi.org/10.1016/s0006-291x(83)80109-0 · DOI
Richard V, Dodson GG, Mauguen Y (1993) Human deoxyhaemoglobin-2,3-diphosphoglycerate complex low-salt structure at 2.5 A resolution. J Mol Biol 233:270–274. https://doi.org/10.1006/jmbi.1993.1505 · DOI
Rieder RF, Oski FA, Clegg JB (1969) Hemoglobin Philly (beta 35 tyrosine phenylalanine): studies in the molecular pathology of hemoglobin. J Clin Invest 48:1627–1642. https://doi.org/10.1172/JCI106128 · DOI
Riemer C, ElSherbini A, Stojanovic N et al (1998) A database of experimental results on globin gene expression. Genomics 53:325–337. https://doi.org/10.1006/geno.1998.5524 · DOI
Safo MK, Abraham DJ (2005) The enigma of the liganded hemoglobin end state: a novel quaternary structure of human carbonmonoxy hemoglobin. Biochemistry 44:8347–8359. https://doi.org/10.1021/bi050412q · DOI
Safo MK, Bruno S (2011) Allosteric effectors of hemoglobin: past, present and future. In: Chemistry and biochemistry of oxygen therapeutics. Wiley, Ltd., pp 285–300
Safo MK, Moure CM, Burnett JC et al (2001) High–resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector. Protein Sci 10:951–957 · DOI
Safo MK, Boyiri T, Burnett JC et al (2002a) X-ray crystallographic analyses of symmetrical allosteric effectors of hemoglobin: compounds designed to link primary and secondary binding sites. Acta Crystallogr D Biol Crystallogr 58:634–644. https://doi.org/10.1107/s0907444902002627 · DOI
Safo MK, Burnett JC, Musayev FN et al (2002b) Structure of human carbonmonoxyhemoglobin at 2.16 Å: a snapshot of the allosteric transition. Acta Crystallographica Section D 58:2031–2037. https://doi.org/10.1107/S0907444902015809 · DOI
Safo MK, Abdulmalik O, Danso-Danquah R et al (2004) Structural basis for the potent antisickling effect of a novel class of five-membered heterocyclic aldehydic compounds. J Med Chem 47:4665–4676. https://doi.org/10.1021/jm0498001 · DOI
Safo MK, Abdulmalik O, Lin HR et al (2005) Structures of R- and T-state hemoglobin Bassett: elucidating the structural basis for the low oxygen affinity of a mutant hemoglobin. Acta Crystallogr D Biol Crystallogr 61:156–162. https://doi.org/10.1107/S0907444904030501 · DOI
Safo MK, Ahmed MH, Ghatge MS, Boyiri T (2011) Hemoglobin-ligand binding: understanding Hb function and allostery on atomic level. Biochim Biophys Acta 1814:797–809. https://doi.org/10.1016/j.bbapap.2011.02.013 · DOI
Safo MK, Ko T-P, Abdulmalik O et al (2013) Structure of fully liganded Hb ζ2β2s trapped in a tense conformation. Acta Crystallogr D Biol Crystallogr 69:2061–2071. https://doi.org/10.1107/S0907444913019197 · DOI
Safo MK, Ko T-P, Schreiter ER, Russell JE (2015) Structural basis for the antipolymer activity of Hb ζ2β2s trapped in a tense conformation. J Mol Struct 1099:99–107. https://doi.org/10.1016/j.molstruc.2015.06.047 · DOI
Sahu SC, Simplaceanu V, Gong Q et al (2007) Insights into the solution structure of human deoxyhemoglobin in the absence and presence of an allosteric effector. Biochemistry 46:9973–9980. https://doi.org/10.1021/bi700935z · DOI
Sakuragawa M, Ohba Y, Miyaji T et al (1984) A Japanese boy with hemolytic anemia due to an unstable hemoglobin (Hb Bristol). Nippon Ketsueki Gakkai Zasshi 47:896–902
Samaja M, Rovida E, Niggeler M et al (1987) The dissociation of carbon monoxide from hemoglobin intermediate. J Biol Chem 262:4528–4533 · DOI
Samuni U, Dantsker D, Juszczak LJ et al (2004) Spectroscopic and functional characterization of T state hemoglobin conformations encapsulated in silica gels. Biochemistry 43:13674–13682. https://doi.org/10.1021/bi048531d · DOI
Sawicki CA, Gibson QH (1976) Quaternary conformational changes in human hemoglobin studied by laser photolysis of carboxyhemoglobin. J Biol Chem 251:1533–1542 · DOI
Sawicki CA, Gibson QH (1978) The relation between carbon monoxide binding and the conformational change of hemoglobin. Biophys J 24:21–33. https://doi.org/10.1016/S0006-3495(78)85328-4 · DOI
Schneider RG, Atkins RJ, Hosty TS et al (1975) Haemoglobin Titusville: alpha94 Asp replaced by Asn. a new haemoglobin with a lowered affinity for oxygen. Biochim Biophys Acta 400:365–373 · DOI
Schoenborn BP (1976) Dichloromethane as an antisickling agent in sickle cell hemoglobin. Proc Natl Acad Sci USA 73:4195–4199. https://doi.org/10.1073/pnas.73.11.4195 · DOI
Schumacher MA, Dixon MM, Kluger R et al (1995) Allosteric transition intermediates modelled by crosslinked haemoglobins. Nature 375:84–87. https://doi.org/10.1038/375084a0 · DOI
Schumacher MA, Zheleznova EE, Poundstone KS et al (1997) Allosteric intermediates indicate R2 is the liganded hemoglobin end state. Proc Natl Acad Sci USA 94:7841–7844. https://doi.org/10.1073/pnas.94.15.7841 · DOI
Sharma VS, Newton GL, Ranney HM et al (1980) Hemoglobin Rothschild (beta 37(C3)Trp replaced by Arg): a high/low affinity hemoglobin mutant. J Mol Biol 144:267–280. https://doi.org/10.1016/0022-2836(80)90090-x · DOI
Shaw E, Scott C, Suh J et al (2003) RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the radiation therapy oncology group recursive partitioning analysis brain metastases database. J Clin Oncol 21:2364–2371. https://doi.org/10.1200/JCO.2003.08.116 · DOI
Shibayama N, Saigo S (2001) Direct observation of two distinct affinity conformations in the T state human deoxyhemoglobin. FEBS Lett 492:50–53. https://doi.org/10.1016/s0014-5793(01)02225-6 · DOI
Shibayama N, Miura S, Tame JRH et al (2002) Crystal structure of horse carbonmonoxyhemoglobin-bezafibrate complex at 1.55-A resolution. a novel allosteric binding site in R-state hemoglobin. J Biol Chem 277:38791–38796. https://doi.org/10.1074/jbc.M205461200 · DOI
Silva MM, Rogers PH, Arnone A (1992) A third quaternary structure of human hemoglobin A at 1.7-A resolution. J Biol Chem 267:17248–17256 · DOI
Smith FR, Simmons KC (1994) Cyanomet human hemoglobin crystallized under physiological conditions exhibits the Y quaternary structure. Proteins 18:295–300. https://doi.org/10.1002/prot.340180310 · DOI
Smith FR, Lattman EE, Carter CW (1991) The mutation beta 99 Asp-Tyr stabilizes Y-a new, composite quaternary state of human hemoglobin. Proteins 10:81–91. https://doi.org/10.1002/prot.340100202 · DOI
Song X, Simplaceanu V, Ho NT, Ho C (2008) Effector-induced structural fluctuation regulates the ligand affinity of an allosteric protein: binding of inositol hexaphosphate has distinct dynamic consequences for the T and R states of hemoglobin. Biochemistry 47:4907–4915. https://doi.org/10.1021/bi7023699 · DOI
Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4:397–407. https://doi.org/10.1038/nrm1103 · DOI
Srinivasan R, Rose GD (1994) The T-to-R transformation in hemoglobin: a reevaluation. PNAS 91:11113–11117. https://doi.org/10.1073/pnas.91.23.11113 · DOI
Stern W, Mathews D, McKew J et al (2012) A phase 1, first-in-man, dose-response study of Aes-103 (5-HMF), an anti-sickling, allosteric modifier of hemoglobin oxygen affinity in healthy norman volunteers. Blood 120:3210–3210 · DOI
Stucker O, Laurent D, Duvelleroy M et al (1985) Incorporation of inositol hexaphosphate in stored erythrocytes: effect on tissue oxygenation. Life Support Syst 3(Suppl 1):458–461
Sun DP, Zou M, Ho NT, Ho C (1997) Contribution of surface histidyl residues in the alpha-chain to the Bohr effect of human normal adult hemoglobin: roles of global electrostatic effects. Biochemistry 36:6663–6673. https://doi.org/10.1021/bi963121d · DOI
Sun K, D’Alessandro A, Ahmed MH et al (2017) Structural and functional insight of sphingosine 1-phosphate-mediated pathogenic metabolic reprogramming in sickle cell disease. Sci Rep 7:15281. https://doi.org/10.1038/s41598-017-13667-8 · DOI
Szabo A, Karplus M (1972) A mathematical model for structure-function relations in hemoglobin. J Mol Biol 72:163–197. https://doi.org/10.1016/0022-2836(72)90077-0 · DOI
Torrance J, Jacobs P, Restrepo A et al (1970) Intraerythrocytic adaptation to anemia. N Engl J Med 283:165–169. https://doi.org/10.1056/NEJM197007232830402 · DOI
Traylor TG, Deardurff LA, Coletta M et al (1983) Reactivity of ferrous heme proteins at low pH. J Biol Chem 258:12147–12148 · DOI
Vasseur C, Blouquit Y, Kister J et al (1992) Hemoglobin Thionville. An alpha-chain variant with a substitution of a glutamate for valine at NA-1 and having an acetylated methionine NH2 terminus. J Biol Chem 267:12682–12691 · DOI
Vichinsky E, Hoppe CC, Ataga KI et al (2019) A phase 3 randomized trial of Voxelotor in sickle cell disease. N Engl J Med 381:509–519. https://doi.org/10.1056/NEJMoa1903212 · DOI
Wilson J, Phillips K, Luisi B (1996) The crystal structure of horse deoxyhaemoglobin trapped in the high-affinity (R) state. J Mol Biol 264:743–756. https://doi.org/10.1006/jmbi.1996.0674 · DOI
Winslow RM, Charache S (1975) Hemoglobin Richmond. Subunit dissociation and oxygen equilibrium properties. J Biol Chem 250:6939–6942 · DOI
Winter PM, Miller JN (1976) Carbon monoxide poisoning. JAMA 236:1502–1504. https://doi.org/10.1001/jama.1976.03270140054029 · DOI
Wireko FC, Abraham DJ (1991) X-ray diffraction study of the binding of the antisickling agent 12C79 to human hemoglobin. Proc Natl Acad Sci USA 88:2209–2211. https://doi.org/10.1073/pnas.88.6.2209 · DOI
Wireko FC, Kellogg GE, Abraham DJ (1991) Allosteric modifiers of hemoglobin. 2. Crystallographically determined binding sites and hydrophobic binding/interaction analysis of novel hemoglobin oxygen effectors. J Med Chem 34:758–767. https://doi.org/10.1021/jm00106a042 · DOI
Woods JA, Storey CJ, Babcock EE, Malloy CR (1998) Right-shifting the oxyhemoglobin dissociation curve with RSR13: effects on high-energy phosphates and myocardial recovery after low-flow ischemia. J Cardiovasc Pharmacol 31:359–363. https://doi.org/10.1097/00005344-199803000-00005 · DOI
Xu GG, Deshpande TM, Ghatge MS et al (2015) Design, synthesis, and investigation of novel nitric oxide (NO)-releasing prodrugs as drug candidates for the treatment of ischemic disorders: insights into NO-releasing prodrug biotransformation and hemoglobin-NO biochemistry. Biochemistry 54:7178–7192. https://doi.org/10.1021/acs.biochem.5b01074 · DOI
Xu GG, Pagare PP, Ghatge MS et al (2017) Design, synthesis, and biological evaluation of ester and ether derivatives of antisickling agent 5-HMF for the treatment of sickle cell disease. Mol Pharm 14:3499–3511. https://doi.org/10.1021/acs.molpharmaceut.7b00553 · DOI
Yokoyama T, Neya S, Tsuneshige A et al (2006) R-state haemoglobin with low oxygen affinity: crystal structures of deoxy human and carbonmonoxy horse haemoglobin bound to the effector molecule L35. J Mol Biol 356:790–801. https://doi.org/10.1016/j.jmb.2005.12.018 · DOI
Yonetani T, Kanaori K (2013) How does hemoglobin generate such diverse functionality of physiological relevance? Biochim Biophys Acta 1834:1873–1884. https://doi.org/10.1016/j.bbapap.2013.04.026 · DOI
Yonetani T, Tsuneshige A (2003) The global allostery model of hemoglobin: an allosteric mechanism involving homotropic and heterotropic interactions. CR Biol 326:523–532. https://doi.org/10.1016/S1631-0691(03)00150-1 · DOI
Yonetani T, Park S-I, Tsuneshige A et al (2002) Global allostery model of hemoglobin. Modulation of O(2) affinity, cooperativity, and Bohr effect by heterotropic allosteric effectors. J Biol Chem 277:34508–34520. https://doi.org/10.1074/jbc.M203135200 · DOI
Youssef AM, Safo MK, Danso-Danquah R et al (2002) Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin. J Med Chem 45:1184–1195. https://doi.org/10.1021/jm010358l · DOI
Zago MA, Bottura C (1983) Splenic function in sickle-cell diseases. Clin Sci 65:297–302. https://doi.org/10.1042/cs0650297 · DOI
Zaugg RH, Walder JA, Klotz IM (1977) Schiff base adducts of hemoglobin. Modifications that inhibit erythrocyte sickling. J Biol Chem 252:8542–8548 · DOI
Zhang Y, Berka V, Song A et al (2014) Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression. J Clin Invest 124:2750–2761. https://doi.org/10.1172/JCI74604 · DOI

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“A low Hb level means a decreased oxygen transport capacity, which may lead to tissue hypoxia, cause damage to the gastrointestinal mucosa, increase the risk of bleeding, and afect postoperative rehabilitation [20].”
The discovery of hemoglobin body: a start to more
Zhang, B., Yang, Y., Zhu, Y., Zhang, S., Huang, H., & Sun, Q. (2024) · Precision Nutrition · doi:10.1097/pn9.0000000000000071 · Cited by 1
Study of Alloimmunization in Transfusion-dependent Thalassemia Patients at a Tertiary Care Hospital
Aishwarya, M., Patil, S. Y., & Haridas, A. (2024) · Journal of Applied Hematology · doi:10.4103/joah.joah_26_24 · Cited by 2
Fatores associados à falha de extubação em unidade de terapia intensiva: estudo de caso-controle
Arcanjo, A. B. B., & Beccária, L. M. (2023) · Revista Latino-Americana de Enfermagem · doi:10.1590/1518-8345.6224.3865 · Cited by 3
“Outro fator relacionado ao desmame ventilatório e período periextubação é a hemoglobina que, quando em níveis mais baixos (inferior a 10,0 g/dL), prevê a falha de extubação, pois reduz a capacidade de carregar oxigênio, comprometendo o metabolismo aeróbico da musculatura respiratória e resultando em insuficiência resp…”
Background
Hematological Status of Broilers with Addition Pegagan (Centella asiatica (L.) Urban) on Feed in Maintenance Without Vaccination
Herwintono, H., Hidayati, A., & Khotimah, K. (2023) · Scholars Journal of Agriculture and Veterinary Sciences · doi:10.36347/sjavs.2023.v10i07.002 · Cited by 2
“This is by the opinion of Ahmed et al., (2020) blood hemoglobin levels are determined by body activity, the higher the body's activity the higher the hemoglobin level. Protein contained in feed influences the formation of hemoglobin, because protein is an important component in the formation of blood cells. Wulandari…”
BackgroundMethodInfluential
SERS of Human Red Blood Cells in Non-Resonant Conditions: Benefits, Limitations, and Complementary Tools (CytoViva and GFAAS)
Wells, K. L., Alla, P., Kaiser, K. G., Murgulet, I. T., Adragna, N., & Pavel, I. (2023) · Chemosensors · doi:10.3390/chemosensors11070353 · Cited by 2
A Pharmacometrics Model to Characterize a New Type of Target-Mediated Drug Disposition (TMDD) – Nonlinear Pharmacokinetics of Small-Molecule PF-07059013 Mediated By Its High-capacity Pharmacological Target Hemoglobin With Positive Cooperative Binding
Xu, M., & An, G.-H. (2023) · AAPS Journal · doi:10.1208/s12248-023-00808-3 · Cited by 2
“Hemoglobin is a tetramer macromolecule that includes two α-chains (α1 and α2) and two β-chains (β1 and β2) [1, 3].”
Invitro impact of a combination of red and infrared LEDs, infrared laser and magnetic field on biomarkers of oxidative stress and hemolysis of erythrocytes sampled from healthy individuals and diabetes patients
Kurhaluk, N., Ткаченко, Г. М., & Tomin, V. I. (2023) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2023.112685 · Cited by 4
Physiological Roles, not Structure will Categorize Placement of Molecules in Humours (Akhlat) in Unani Medicine: The Case of Human Haemoglobin
Rizvi, A., & Sherani, F. (2022) · Advanced Chemicobiology Research · doi:10.37256/acbr.1220221465 · Cited by 2
“These interactions include hydrophobic interactions, hydrogen bonds and some salt bridges [9].”
Background
A hemoglobin-based nanozyme with ruthenium-induced nanomotor ability exhibiting photothermal and chemodynamic responses
Coban, G., Çetin, E. A., Gök, İ. Y., Kaya, N. B., Kapucu, B. G., Onur, M. A., Polat, M., Kip, Ç., & Tuncel, A. (2026) · Microchimica Acta · doi:10.1007/s00604-026-08176-3 · Cited by 1
“Each heme group of Hb contains a porphyrin ring [ 22 ].”
Influential
Haemoglobin polymorphism in different blood levels of Ethiopian Zebu x Holstein Friesian crossbred dairy cattle
Tesfaye, E., Melesse, A., Betsha, S., & Andualem, D. (2026) · PLoS ONE · doi:10.1371/journal.pone.0340009 · Cited by 1
Ischaemia/reperfusion and permanent ischaemia differentially affect haemoglobin properties – Possible influence of oxidative stress and adaptation to acute hypoxia
Bochkova, Z. V., Khlystova, M. A., Katrukha, V. A., Baizhumanov, A., Vasilyeva, K. V., Nosova, A. E., Karhov, A. M., Parshina, E. Y., Solotenkov, M. A., Moshchenko, A., et al. (2026) · The FEBS Journal · doi:10.1111/febs.70453 · Cited by 1
“…this change in Hb may be due to some allosteric conformational modiﬁcation of Hb subunits and possibly due to nitric oxide binding to the Cys-residue of the globin beta-subunit leading to the stabilisation of Hb R-conformation and to the increase in the probability of planar haem conformation [27].”
Effects of low-level lead exposure on hematological parameters and the possible underlying mechanisms
Liao, X., Lin, T., Zhang, Z., He, P., Wu, H., Ouyang, X., Li, Q., Yu, Z., Zhang, Z., Wu, J., et al. (2026) · Environmental Pollution · doi:10.1016/j.envpol.2026.127884 · Cited by 1
Self-assembled chiral structures of meso-tetraarylporphyrins in solutions and liquid crystals
Burmistrov, V., Trifonova, I., Aleksandriiskii, V. V., Novikov, I., Budanova, A. A., Lubimova, T., & Semeikin, A. S. (2025) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2025.128248 · Cited by 1
Functional Requirement of Niacinamide for Blood Profiles, Antioxidant Status, and Intestinal Health in Finishing Pigs Fed a Low-Protein Diet
Zhao, Y., Tang, F., Shi, Y., Tan, Q., Ju, Q., Yang, Z., Yang, G., Gao, P., Kim, S. W., Xi, L., et al. (2025) · Animals · doi:10.3390/ani15121813 · Cited by 1
“In erythrocytes, although mitochondrial respiration is absent, NAD + is essential for glycolysis, enabling ATP production via NAD + -dependent enzymes such as glyceraldehyde-3-phosphate dehydrogenase [31,32].”
The cost-effectiveness of interventions used for the screening, diagnosis and management of anaemia in pregnancy: A systematic review
Allen, C. L., Eddy, K. E., Ginnane, J. F., Cheang, S., Nguyen, R., Scott, N., Vogel, J. P., & McDougall, A. R. A. (2025) · PLOS Global Public Health · doi:10.1371/journal.pgph.0004392 · Cited by 1
“Anaemia is a common haematological condition characterised by an inadequate number of red blood cells and/or inadequate haemoglobin concentration [1,2].”
Association between hemoglobin-to-red blood cell distribution width ratio and cognitive function in older US adults: a cross-sectional study based on the NHANES 2011–2014
Wang, F., Wang, X., Wang, C., Liu, H., Xu, Z., Li, D., Zhao, X., Zhao, J., Li, S., & Zhao, J. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1571159 · Cited by 3
Characterization of Hemoglobin Variants by Capillary Electrophoresis, UV–Vis, and FTIR Spectroscopy
Werle, J., Dunovská, K., Podhájský, J., Cerny, M., Čepová, J., Parikesit, A. A., Bjørklud, G., Kotaška, K., Klapková, E., Průša, R., et al. (2025) · Electrophoresis · doi:10.1002/elps.202400154 · Cited by 5
“A high α -helix content is crucial for the proper functioning of hemoglobin, as it ensures structural integrity and efficient oxygen binding and release [43, 44].”
Cell-free hemoglobin released from hemolysis induces programmed cell death through iron overload and oxidative stress in grass carp (Ctenopharyngodon idella)
Song, J., Li, N., Yang, Y., Chen, B., Hu, J., Tian, Y., Lin, L., & Qin, Z. (2025) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2024.110106 · Cited by 1
A particular focus on the prevalence of α-thalassemia and β-thalassemia among pregnant women in Changsha County, Hunan Province
Xia, Y.-J., Huang, C., Yang, M., Zhang, M., & Lu, Y. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1422462 · Cited by 1
2-Methoxy-4-formylphenol suppresses methylglyoxal glycation mediated structural alterations and esterase activity of hemoglobin - A multi spectroscopic, biophysical and in-silico study.
Esackimuthu, P., Jeevanandam, J., Kumar, B., Murugan, N., & Saraswathi, N. T. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.137128 · Cited by 1
Voxelotor (GBT440) in pediatric sickle cell disease: A review
Jamalapur, S. L., Glaros, A. K., & Ravindranath, Y. (2024) · Pediatric Hematology Oncology Journal · doi:10.1016/j.phoj.2024.07.006 · Cited by 1
Association of hemoglobin-to-red blood cell distribution width ratio and cognition: a cross-sectional study
Zhang, Y., Fang, F., Xi, L., Zhou, J., Xu, P., & Tu, J. (2024) · Archives of Gerontology and Geriatrics Plus · doi:10.1016/j.aggp.2024.100027 · Cited by 1
Single bout of a long-duration running treadmill increases myoglobin but not haemoglobin and interleukin 6 levels in mice (Mus musculus)
Yuliastrid, D., Kusnanik, N. W., Purwanto, B., Noordia, A., Purwoto, S. P., & Pranoto, A. (2023) · Comparative Exercise Physiology · doi:10.1163/17552559-20220075 · Cited by 1
Immunological Profile of Patients with Controlled and Uncontrolled Type 2 Diabetes Melitus in Mataram City, West Nusa Tenggara
Arjita, I. P. D., Adnyana, I. G. A., Anulus, A., Saputra, I. P. B. A., & Diarti, M. W. (2023) · JURNAL INFO KESEHATAN · doi:10.31965/infokes.vol21.iss2.933
Exploring the moderating effects of SIRT1 and gene polymorphisms rs7895833 on the relationship between hemoglobin levels and physical frailty in elderly adults with comorbid chronic diseases: A moderated mediation analysis
Ardinata, D., Harahap, N. S., Lubis, N. D. A., & Nasution, T. A. (2023) · F1000Research · doi:10.12688/f1000research.133517.3 · Cited by 1
“14 Low hemoglobin levels, known as anemia, are a common condition in older adults and can be caused by a variety of factors, including nutritional deficiencies, chronic diseases, and medications 15 which can lead to a decrease in physical function and an increased risk of frailty.”
Background
Exploring the moderating effects of SIRT1 protein expression and gene polymorphisms rs7895833 on the relationship between hemoglobin levels and physical frailty in elderly adults with comorbid chronic diseases: A moderated mediation analysis
Ardinata, D., Harahap, N. S., Lubis, N. D. A., & Nasution, T. A. (2023) · F1000Research · doi:10.12688/f1000research.133517.1 · Cited by 1
Muscle oxygen utilization and ventilatory parameters during exercise in people with cystic fibrosis: Role of HbA1c
Quertermous, B., Seigler, N., Looney, J., Crandall, R., Simon, A. B., Blackburn, M., Derella, C. C., Blanks, A. M., Mckie, K., Forseen, C., et al. (2023) · Chronic Respiratory Disease · doi:10.1177/14799731231174542 · Cited by 1
A New Case of Hb Headington ( HBB : c.217A>C) Due to a New DNA Transversion, Found in a Patient with Type 2 Diabetes Mellitus
Liu, Y., Liu, B., Qiao, Y., & Niu, W.-Y. (2022) · Hemoglobin · doi:10.1080/03630269.2022.2067044 · Cited by 8
“However, the measurement of Hb A1c may interfere with particular Hb variants that include the change of charge or structure of the Hb [3,4].”
Background
Efektivitas Komsumsi Labu Siam Terhadap Peningkatan Hemoglobin pada Ibu Hamil
Wahyuni, N. I., & Sukmawati (2021) · JURNAL ANTARA KEBIDANAN · doi:10.37063/jurnalantarakebidanan.v4i3.318 · Cited by 1
Tetramerisation governs SALL transcription factor function in development and disease
Giuliani, S., Chhatbar, K., Wear, M., Guy, J., Mathieson, T., Burdett, H., George, L., Alston, G., Spanos, C., McHugh, T., et al. (2025) · bioRxiv · doi:10.1101/2025.10.27.684836
Spectroscopic and computational studies on biophysical aspects of ivermectin binding with human hemoglobin: thermodynamics and structural insights
Prabhavathi, M., Lavanya, K., Raju, B. S., Chowdhury, R., & Sahoo, B. (2026) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-026-00970-8
“With respect to the functional aspect of Hb, it transports oxygen to different tissues besides its important role as a blood buffer by binding with excess hydronium ions at specific amino acid residues especially histidine with regulating the physiological pH homeostasis [5, 6].”
Oxidative and Haemolytic Properties of Aqueous Extract of Pennisetum purpureum Shoots as Remedy to Sickle Cell Disease
I., O. U., C., I., N., O. G., N., B. R., D., C. N., D., O., M., J. S., F., G. M., H., A. A., Ananians, A., et al. (2026) · African Journal of Biochemistry and Molecular Biology Research · doi:10.58578/ajbmbr.v3i3.12236
The journey beyond hemoglobin: A bibliometric approach to review the biomarkers for sickle cell disease
Hassan, M. S., Hoque, M., & Ali, S. (2026) · Gene Reports · doi:10.1016/j.genrep.2026.102662
A Novel α-Globin Gene Variant: Hb Romagna [α61(E10)Lys>Gln; HBA1:c.184A>C] Co-Inherited with Hb A2-Lampang [δ47(CD6)Asp>Asn; HBD:c.142G>A] in an Italian Diabetic Woman
Rosetti, M., Poletti, G., Olivieri, M., Mogni, M., Maffei, M., Noemi, A., Raffaele, P., Maoggi, S., Coviello, D., & Ivaldi, G. (2026) · Thalassemia Reports · doi:10.3390/thalassrep16030016
Interactions of nanoplastics with human albumin and hemoglobin: Structural and spectroscopic insights
Ibrahim, B., Permana, R., Oyehan, T. A., Ezeorba, T. P. C., & Valsami‐Jones, E. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.153921
Identification, functional characterization of a novel flavohemoglobin from Ensifer adhaerens and its application to enhancing vitamin B12 production
Zhu, J. F., Wang, S. Q., Li, B., Wang, B., Wang, P., Wu, J., & Wang, Z. (2026) · Microbial Cell Factories · doi:10.1186/s12934-026-03073-z
“Flavohemoprotein and hemoglobin share high degree of sequence and structural similarity in their globin domain [30, 31].”
Entanglement enables coherence transfer and feedforward corrects the state in quantum teleportation on superconducting dynamic circuits
Rai, V., & Farhat, S. (2026) · Scientific Reports · doi:10.1038/s41598-026-63793-5
“The choice of this encoding follows the two-state allosteric model of haemoglobin, in which the tense (T, deoxygenated) and relaxed (R, oxygenated) conformations are taken as the two basis states and the rotation angle sets their population ratio 15,16 .”
Phenylmercury induces structural and functional alterations on hemoglobin: From isolated protein to a biological model.
de Souza, S. O., Sales, M. V. D. S., Queiroz, M., Lima, A. F. S., Dias, W. D. S., Oliveira, L. F. A. D. M., da Silva, J. A. G., da Silva, J. C. S., Fonseca, E. J. D. S., Anderson, L., et al. (2026) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2026.143001
Association between high maternal haemoglobin levels in the first trimester and gestational diabetes mellitus: a prospective birth cohort study
Li, W., Yang, J., Li, H.-B., Sun, B., Wu, Z.-Q., Gao, H., Liu, W.-J., Xu, L., & Zhu, Y.-B. (2026) · Journal of Global Health · doi:10.7189/jogh.16.04212
“Haemoglobin is a key indicator of oxygen-carrying capacity, and its levels are influenced by iron homeostasis, plasma volume expansion, and erythropoiesis [ 8 , 9 ].”
β-globin mediates antimicrobial defense and inflammatory regulation in common carp (Cyprinus carpio).
Cui, X.-Y., Zhao, C.-F., Jin, Z., Liu, Y.-C., Li, L., Zhao, X., & Kong, X.-H. (2026) · Fish and Shellfish Immunology · doi:10.1016/j.fsi.2026.111571
Coagulation-Friendly Environment in Cardiac Surgery: A Narrative Review.
Yévenes, F., Bolliger, D., Dedda, U. D., Ahmed, A. B., Koller, T., Unić-Stojanović, D., & Lancé, M. (2026) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2026.07.016
Thermodynamic Frontiers in Hemoglobin‐Inspired Polymer Science for Diagnosis and Modulation of Neurodegenerative Diseases
Edrisi, M., & Rabiee, N. (2026) · Cell Biochemistry and Function · doi:10.1002/cbf.70261
“Just as hemoglobin toggles between tense and relaxed states in response to oxygen tension or pH shifts, these polymers can be engineered to respond to local pathological cues such as redox stress, acidity, or the presence of β‐sheet‐rich intermediates [71].”
First Report of Co‐Inheritance of Hemoglobin British Columbia ( HBB :c. 304G >A) and β‐Thalassemia IVS ‐I‐6 ( HBB :c.92+ 6T >C): Clinical Characterization of an Iranian Case
Fathalizade, K., Bigdeli, M. K., Eghbali, S. S., Ghiyasi, M., Rastgoo, R., & Mousavi, M. J. (2026) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.70261
Learning residue-level context for modeling protein-protein interactionsPreprint
Zhang, Z., Yang, Z., Liu, A., Yu, K., Zhao, J., Yang, Y., Neale, B. M., & Chen, S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.01.729118
“40,41 Together, these analyses demonstrate that ReCLIP can distinguish clinically pathogenic from benign variants, identify disease-relevant perturbations across molecular interaction contexts, and provide mechanistic insight into how genetic variation alters protein interactions through both…”
Origins of allostery in vertebrate hemoglobin evolutionPreprint
Cortez-Romero, C. R., Bautista, N. M., Nisler, C. R., Muñiz-Trejo, R., Storz, J. F., & Thornton, J. W. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.25.727495
CgHb-like modulates the energy metabolism, histone acetylation and inflammatory responses in oysters during Vibrio splendidus stimulation
Wang, J., He, M., Leng, J., Zhang, J., Chang, R., Shan, W., Shi, X., Li, Y., Sun, J., & Song, L. (2026) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2026.111431 · Cited by 1
Molecular profiles of red blood cells across geographic, pathological, and age-related perspectives: translational insights
Almadhaani, K. Y., Altaie, A., & Hamoudi, R. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1798592
“This process is regulated by several molecular factors that influence hemoglobin function (34, 35, 56).”
Influential
COMPREHENSIVE REVIEW OF GENETIC AND EPIGENETICS REGULATION OF FETAL HEMOGLOBIN IN β-HEMOGLOBINOPATHIES: FROM MOLECULAR MECHANISMS TO CLINICAL APPLICATIONS
Za’ror, Y. S. M. A., Suleiman, J. B., Delmani, F. A., Alhmoud, J. F., Ayasreh, A. M., Al-wendawi, S. I., & Azlan, M. (2026) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2026.046
Valorization of turkey cruor through peptic hydrolysis: peptidomic and machine learning approaches for the identification of antimicrobial peptides.
Fliss, H., Bazinet, M., García-Vela, S., Thibodeau, J., Bazinet, L., & Mikhaylin, S. (2026) · Food Chemistry · doi:10.1016/j.foodchem.2026.149124
Mechanistic Insight into Conformational Control of Enzyme Activity by Genetically Encoded Metal‐Responsive Switches
Payal, Thirman, J., Edmonds, K., Mishra, S., Blackwell, N., Zubi, Y. S., Roux, B., & Lewis, J. C. (2026) · ChemBioChem · doi:10.1002/cbic.70349
“For example, hemoglobin undergoes a well-characterized conformational change in response to oxygen binding, which alters its affinity and enables cooperative binding of subsequent oxygen molecules [5].”
Assessment of Neutrophil Gelatinase Gelatinase-Associated Lipocalin Analysis for Renal Insufficiency in Iraqi β-Thalassemia Major Patients in Karama/Hospital Baghdad
Alwan, E. S., Juda, T., & Majed, L. (2026) · Medical Journal of Babylon · doi:10.4103/mjbl.mjbl_185_23
Hb Thessaloniki, a Novel, Hyperunstable, Alpha Globin Variant Detected in Northern Greece
Boutou, E., Papandreou, N., Mantzou, G., Vlachaki, E., Vyzantiadis, A., Chassanidis, C., Dimopoulou, M., Balassopoulou, A., & Theodoridou, S. (2026) · Hematology Reports · doi:10.3390/hematolrep18020017
“H [18].”
Spermine: A Hemoglobin Modifier That Reduces Autoxidation and Regulates Oxygen Delivery
Shu, P.-L., Chu, Z., You, G.-X., Li, W.-D., Chen, Y.-Z., Jin, H., Zhou, H., Wang, Y., & Zhao, L. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27031197
“It is evidenced by a significant decrease in the size of the β -cleft of HbA, primarily consisting of β 1H146 and β 2H146 [53].”
Can severe anaemia limit carbon dioxide clearance under acute carbon dioxide load
Gnanarathne, S., Ratnayake, A., & Isurindi, U. A. (2026) · Medical Hypotheses · doi:10.1016/j.mehy.2025.111854
Hemoglobin Phenotype Distribution Among Future Healthcare Providers: A Descriptive Cross‐Sectional Study at a Ghanaian Health Sciences University
Duneeh, R., Ama, D. S. Y., Klugah, M. A., Allotey, E., Akorsu, E. E., Kwadzokpui, P. K., & Ablordey, K. (2026) · TheScientificWorldJournal · doi:10.1155/tswj/1199349
“Hemoglobin, the oxygen-carrying protein in red blood cells, is characterized by signi ﬁ cant genetic diversity across human populations, a phenomenon re ﬂ ecting evolutionary adaptations to environmental pressures like malaria [1].”
Low perioperative hemoglobin as an independent detrimental predictor of functional outcome after basal ganglia hemorrhage: development and validation of a composite prognostic model
Li, X., Zhang, L., Yang, Z., Ding, J., Yu, Y.-F., Yang, S., Duan, F., & Dong, Y. (2025) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2025.1745109
The mediating role of grip strength in the association between hemoglobin and depressive symptoms among older adults
Wang, W., Zhang, Y., Fang, F., Li, Q., Tu, J., & Xi, L. (2025) · Geriatric Nursing · doi:10.1016/j.gerinurse.2025.103770
Mathematical models of iron metabolism: structure and functions
Melchenko, N. I., & Akberdin, I. R. (2025) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vjgb-25-108
Monitoring Inhibition of Hemoglobin Peroxidase Activity After Exposure to Cigarette Smoke Using an Electrochemical Biosensor
Sequeda-Juárez, A., Cortés-Ortegón, F., Ortega-Picazo, D., García-García, J. A., Espinosa-García, A. M., & Sanchez-Perez, C. A. (2025) · Biosensors · doi:10.3390/bios15120767
“…a multifunctional molecule involved in various processes, including catalytic functions (such as nitrite reductase, dioxygenase, monooxygenase, alkyl hydroperoxidase, esterase, and lipoxygenase activities), nitric oxide metabolism, metabolic reprogramming, pH regulation, and redox homeostasis [2].”
Light-up nanostructures with allosteric DNA mimics of GFPPreprint
Zhang, T., Qian, X., Zhang, J., Cui, H., Bai, T., Wang, W., Wang, Y., Gao, Z., Han, D., Zeng, W., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.10.664110
The Predictive Value of Hemoglobin-to-Red Blood Cell Distribution Width Ratio for the Prognosis of Patients with Aortic Dissection: Based on the Medical Information Mart for Intensive Care-IV Database
Wu, J.-Q., & Zou, Z. (2025) · Anatolian journal of cardiology · doi:10.14744/anatoljcardiol.2025.5415
“49 A relatively small retrospective study sug - gested that a drop in Hb in hospitalized patients with acute stroke may be linked with dismal outcomes, 50 while another study on atrial fibrillation confirmed the presence of ane - mia; even mild anemia (males: 10 ≤ Hb < 13g/dL and females: 10 ≤ Hb <…”
Exploring the Hemoglobin T to R2 Path Using Gaussian Elastic Network Correlation Map Distance
Valenci, Y., & Tobi, D. (2025) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.70014
“Additionally, Several works suggested discrete multi-states along the T → R2 transition [32–34], which is expected since proteins are flexible entities (for review, see [35]).”
Non-Invasive Blood Oxygen Level Monitoring Using Bio-Impedance
Tom, N., Heydari, F., & Yuce, M. R. (2025) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc58623.2025.11254485
“Each hemoglobin molecule contains a heme group featuring ferrous ions, which enables the binding of oxygen[13].”
Natural Antioxidants Effect on the Performance of Erythrocytes, Leucocytes, and Hb Levels of Pregnant Mice Exposed to the Plastic
Palupi, E. S., Wibowo, E., Puspitasari, I. A. R., & Atang (2024) · Journal of Biota · doi:10.19109/biota.v11i1.23677
De Novo Occurrence of Hb Chile [β28(B10) Leu→Met] in a Korean Boy with Methemoglobinemia
Jung, H. J., Kim, B., Kim, H., & Lee, M. (2024) · Hemoglobin · doi:10.1080/03630269.2024.2403405
“Hb contains ferrous iron (Fe 2+ ) in the heme moiety, which reversibly binds oxygen and transports it from the lungs to the tissues [2].”
Correlation Mineral Water Consumption and Hemoglobin Levels in Adolescent Girls
Putri, G. S. A., Maolida, N., & Sukeksi, A. (2024) · Jurnal Kesehatan · doi:10.26630/jk.v15i2.4573
“In saturated conditions, one gram of hemoglobin may bind 1.34 milliliters of oxygen (Ahmed et al., 2020).”
BackgroundInfluential
Exploring cardiovascular health in children: the influence of Hemoglobin-to-Platelet ratio in contrasting rural and urban communities
Nevill, A. M., Reuter, C., Brand, C., Sehn, A. P., Renner, J. D. P., Lemes, V. B., & Duncan, M. J. (2024) · International Journal of Environmental Health Research · doi:10.1080/09603123.2024.2385673
“Hemoglobin, as a key component of red blood cells, is responsible for transporting oxygen throughout the body, while platelets play a crucial role in maintaining vascular integrity and regulating blood flow (Furie and Furie 2005; Ahmedm et al. 2020).”
Coinherited Hemoglobin Lansing-Ramathibodi/Southeast Asian Deletional α0-thalassemia and Hemoglobin E Causing Falsely Low Oxygen Saturation on Pulse Oximetry
Chouymankong, K., Arkarattanakul, N., Mankhemthong, K., Sirinam, N., Phusua, A., Fanhchaksai, K., & Charoenkwan, P. (2024) · Biomedical Sciences and Clinical Medicine · doi:10.12982/bscm.2024.24
Effect of Degree of Smoking Based on Brinkman Index on Hemoglobin Levels in Adults
Wijaya, B. A., & Nataprawira, S. M. (2024) · Community Medicine and Education Journal · doi:10.37275/cmej.v5i2.574
Compliance with Iron Supplementation Consumption in Pregnant Women on Hematological Profiles and Ret-He
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“This final heme will then bind to the globin chain which then forms hemoglobin (Ahmed, Ghatge, and Safo 2020; Farid and Lecat 2019).”
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Potential Impact of Anemia on BALB/c Mice Exposed to an Extremely Low Frequency 50 Hz Magnetic Field with an Intensity of 100 μT and 500 μT
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“One of its main functions is to bind oxygen and spread it throughout the body (Ahmed et al., 2020).”
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“The primary role of hemoglobin is to transport oxygen from the lungs to tissues, binding and releasing oxygen (Ahmed et al., 2020).”
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Background
What geometrically constrained folding models can tell us about real-world protein contact maps
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“hemoglobin) [1], signal transduction (e.”

Authors: Ahmed, M. H., Ghatge, M. S., & Safo, M. K.
Affiliations: Virginia Commonwealth University (US)
Corresponding author: Safo, Martin K.
ORCID: Ahmed, Mostafa H.
Ghatge, Mohini S.
Safo, Martin K.
Venue: Subcellular Biochemistry
Publisher: Springer International Publishing
Published: 2020
Volume: 94
Pages: 345-382
ISSN: 0306-0225 (ISSN-L)
2542-8810
DOI: 10.1007/978-3-030-41769-7_14
PMC: PMC7370311
OpenAlex: W3011621712
Cited by: 317
References: 202
Citations by year: 2026: 65 · 2025: 72 · 2024: 63 · 2023: 60 · 2022: 34 · 2021: 21 · 2020: 2
FWCI: 48.58
Type: book chapter
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Sub-cellular biochemistry/Subcellular biochemistry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (1s10od021756-01a1)
National Institute on Minority Health and Health Disparities (R01MD009124)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
Keywords: hemoglobin, allosteric regulation, oxygen binding, oxygen transport, hemoglobin variants, natural mutation, synthetic ligands, hemoglobin structure
MeSH terms: Allosteric Regulation, Hematologic Diseases, Hemoglobins, Humans, Ligands, Oxygen

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Hemoglobin: Structure, Function and Allostery

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