Metal ions in biological catalysis: from enzyme databases to general principles
Abstract
We analysed the roles and distribution of metal ions in enzymatic catalysis using available public databases and our new resource Metal-MACiE (http://www.ebi.ac.uk/thornton-srv/databases/Metal_MACiE/home.html). In Metal-MACiE, a database of metal-based reaction mechanisms, 116 entries covering 21% of the metal-dependent enzymes and 70% of the types of enzyme-catalysed chemical transformations are annotated according to metal function. We used Metal-MACiE to assess the functions performed by metals in biological catalysis and the relative frequencies of different metals in different roles, which can be related to their individual chemical properties and availability in the environment. The overall picture emerging from the overview of Metal-MACiE is that redox-inert metal ions are used in enzymes to stabilize negative charges and to activate substrates by virtue of their Lewis acid properties, whereas redox-active metal ions can be used both as Lewis acids and as redox centres. Magnesium and zinc are by far the most common ions of the first type, while calcium is relatively less used. Magnesium, however, is most often bound to phosphate groups of substrates and interacts with the enzyme only transiently, whereas the other metals are stably bound to the enzyme. The most common metal of the second type is iron, which is prevalent in the catalysis of redox reactions, followed by manganese, cobalt, molybdenum, copper and nickel. The control of the reactivity of redox-active metal ions may involve their association with organic cofactors to form stable units. This occurs sometimes for iron and nickel, and quite often for cobalt and molybdenum.
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Interaction with metals alters the physicochemical properties of proteins, promoting catalysis of enzymatic reactions, stabilizing protein structure and/or facilitating electron transport.
“The interaction with metals alters the physico- chemical properties of proteins, thereby promoting catalysis of enzymatic reactions, stabilizing protein structure and/or facilitating electron transport 2,3 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [2]
Zinc, iron, and manganese are the transition metals most commonly used as critical cofactors or structural components in mammalian and bacterial proteins.
“Zinc, iron, and manganese are the most common transition metals serving critical cofactor or structural roles in mammalian and bacterial proteins (Andreini et al., 2008).”
From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Andreini et al., 2008
Metal ions, particularly iron, play a critical role in the activity of many enzymes involved in the detoxification of reactive oxygen species.
“One striking example is the critical role of metal ions, particularly iron, in the activity of many enzymes involved in the detoxification of reactive oxygen species (ROS) [54–56].”
From Aprepitant, an antiemetic agent, interferes with metal ion homeostasis of<i>Candida auris</i>and displays potent synergistic interactions with azole drugs (2020) · cites this paper as [56]
Cites
Shannon, R. D. (1976) · Acta Crystallographica Section A · doi:10.1107/s0567739476001551 · Cited by 66,145 · see citing works
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196 · see citing works
KEGG: Kyoto Encyclopedia of Genes and Genomes
Kanehisa, M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.27 · Cited by 37,077 · see citing works
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232 · see citing works
Absolute hardness: companion parameter to absolute electronegativity
Parr, R. G., & Pearson, R. G. (1983) · Journal of the American Chemical Society · doi:10.1021/ja00364a005 · Cited by 7,941 · see citing works
Structural and Functional Aspects of Metal Sites in Biology
Holm, R. H., Kennepohl, P., & Solomon, E. I. (1996) · Chemical Reviews · doi:10.1021/cr9500390 · Cited by 2,536 · see citing works
Dioxygen Activation at Mononuclear Nonheme Iron Active Sites: Enzymes, Models, and Intermediates
Costas, M., Mehn, M. P., Jensen, M. P., & QUE, L. J. (2004) · Chemical Reviews · doi:10.1021/cr020628n · Cited by 2,475 · see citing works
MEROPS: the peptidase database
Rawlings, N. D., & Barrett, A. J. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.325 · Cited by 2,278 · see citing works
The Whole Structure of the 13-Subunit Oxidized Cytochrome c Oxidase at 2.8 Å
Tomitake Tsukihara, A., Aoyama, H., Yamashita, E., Tomizaki, T., Yamaguchi, H., Shinzawa‐Itoh, K., Nakashima, R., Yaono, R., & Yoshikawa, S. (1996) · Science · doi:10.1126/science.272.5265.1136 · Cited by 2,102 · see citing works
The biological chemistry of the elements: the inorganic chemistry of life
(1992) · Choice Reviews Online · doi:10.5860/choice.30-0286 · Cited by 1,326 · see citing works
High-Valent Iron(IV)–Oxo Complexes of Heme and Non-Heme Ligands in Oxygenation Reactions
Nam, W. (2007) · Accounts of Chemical Research · doi:10.1021/ar700027f · Cited by 1,172 · see citing works
The Biological Chemistry of the Elements: The Inorganic Chemistry of Life
Fraústo da Silva, J. J. R., & Williams, R. J. P. (2001) · doi:10.1093/oso/9780198508472.001.0001 · Cited by 1,005 · see citing works
Structure and mechanism of copper, zinc superoxide dismutase
Tainer, J. A., Getzoff, E. D., Richardson, J. S., & Richardson, D. C. (1983) · Nature · doi:10.1038/306284a0 · Cited by 967 · see citing works
BRENDA, the enzyme database: updates and major new developments
Schomburg, I. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh081 · Cited by 952 · see citing works
Calcium signaling: A tale for all seasons
Carafoli, E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032427999 · Cited by 845 · see citing works
The Many Faces of Vitamin B12: Catalysis by Cobalamin-Dependent Enzymes
Banerjee, R. V., & Ragsdale, S. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161828 · Cited by 795 · see citing works
The model organism as a system: integrating 'omics' data sets
Joyce, A. R., & Palsson, B. Ø. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1857 · Cited by 790 · see citing works
The catalytic mechanism of carbonic anhydrase: implications of a rate-limiting protolysis of water
Silverman, D. N., & Lindskog, S. F. (1988) · Accounts of Chemical Research · doi:10.1021/ar00145a005 · Cited by 748 · see citing works
Structural basis of the action of thermolysin and related zinc peptidases
Matthews, B. W. (1988) · Accounts of Chemical Research · doi:10.1021/ar00153a003 · Cited by 687 · see citing works
Electron tunneling through proteins
Gray, H. B., & Winkler, J. R. (2003) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583503003913 · Cited by 667 · see citing works
Magnesium chemistry and biochemistry
Maguire, M. E., & Cowan, J. A. (2002) · BioMetals · doi:10.1023/a:1016058229972 · Cited by 614 · see citing works
Christianson, D. W., & Lipscomb, W. N. (1989) · Accounts of Chemical Research · doi:10.1021/ar00158a003 · Cited by 606 · see citing works
Bertini, I., & Sigel, A. (2001) · CRC Press eBooks · doi:10.1201/9781482270822 · Cited by 577 · see citing works
Self-citationTetrahydropterin-Dependent Amino Acid Hydroxylases
Fitzpatrick, P. F. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.355 · Cited by 514 · see citing works
MEROPS: the peptidase database
Rawlings, N. D. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj089 · Cited by 504 · see citing works
Carbonic Anhydrase: Evolution of the Zinc Binding Site by Nature and by Design
Christianson, D. W., & Fierke, C. A. (1996) · Accounts of Chemical Research · doi:10.1021/ar9501232 · Cited by 476 · see citing works
Lindqvist, Y., Huang, W., Schneider, G., & Shanklin, J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00783.x · Cited by 471 · see citing works
Lesburg, C. A., Zhai, G., Cane, D. E., & Christianson, D. W. (1997) · Science · doi:10.1126/science.277.5333.1820 · Cited by 455 · see citing works
Saito, M. A., Sigman, D. M., & Morel, F. M. M. (2003) · Inorganica Chimica Acta · doi:10.1016/s0020-1693(03)00442-0 · Cited by 440 · see citing works
Roach, P. L., Clifton, I. J., Hensgens, C. M. H., Shibata, N., Schofield, C. J., Hajdu, J., & Baldwin, J. E. (1997) · Nature · doi:10.1038/42990 · Cited by 437 · see citing works
Active-site zinc ligands and activated H2O of zinc enzymes.
Vallée, B. L., & Auld, D. S. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.1.220 · Cited by 434 · see citing works
Managing the manganese: molecular mechanisms of manganese transport and homeostasis
Pittman, J. K. (2005) · New Phytologist · doi:10.1111/j.1469-8137.2005.01453.x · Cited by 377 · see citing works
Mechanism of Fe(III) – Zn(II) Purple Acid Phosphatase Based on Crystal Structures
Klabunde, T., Sträter, N., Fröhlich, R., Witzel, H., & Krebs, B. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0354 · Cited by 365 · see citing works
Mendel, R. R., & Bittner, F. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.03.013 · Cited by 356 · see citing works
Novel non-heme iron center of nitrile hydratase with a claw setting of oxygen atoms
Nagashima, S., Nakasako, M., Dohmae, N., Tsujimura, M., Takio, K., Odaka, M., Yohda, M., Kamiya, N., & Endo, I. (1998) · Nature Structural Biology · doi:10.1038/nsb0598-347 · Cited by 353 · see citing works
Diverse reactions catalyzed by naphthalene dioxygenase fromPseudomonas sp strain NCIB 9816
Resnick, S. M., Lee, K., & Gibson, D. T. (1996) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/bf01574775 · Cited by 318 · see citing works
Mechanism for the Hydrolysis of Organophosphates by the Bacterial Phosphotriesterase
Aubert, S. D., Li, Y., & Raushel, F. M. (2004) · Biochemistry · doi:10.1021/bi0497805 · Cited by 318 · see citing works
A revised mechanism for the alkaline phosphatase reaction involving three metal ions
Stec, B., Holtz, K. M., & Kantrowitz, E. R. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3799 · Cited by 306 · see citing works
Bistability of atmospheric oxygen and the Great Oxidation
Goldblatt, C., Lenton, T. M., & Watson, A. J. (2006) · Nature · doi:10.1038/nature05169 · Cited by 297 · see citing works
A Structure-Based Mechanism for Copper−Zinc Superoxide Dismutase,
Hart, P. J., Balbirnie, M., Ogihara, N. L., Nersissian, A. M., Weiss, M. S., Valentine, J. S., & Eisenberg, D. S. (1999) · Biochemistry · doi:10.1021/bi982284u · Cited by 270 · see citing works
Finding Intermediates in the O2 Activation Pathways of Non-Heme Iron Oxygenases
Kovaleva, E. G., Neibergall, M. B., Chakrabarty, S., & Lipscomb, J. D. (2007) · Accounts of Chemical Research · doi:10.1021/ar700052v · Cited by 246 · see citing works
Solvent Tuning of Electrochemical Potentials in the Active Sites of HiPIP Versus Ferredoxin
Dey, A., Jenney, F. E., Adams, M. W. W., Babini, E., Takahashi, Y., Fukuyama, K., Hodgson, K. O., Hedman, B., & Solomon, E. I. (2007) · Science · doi:10.1126/science.1147753 · Cited by 218 · see citing works
Molecular Details of Urease Inhibition by Boric Acid: Insights into the Catalytic Mechanism
Benini, S., Rypniewski, W. R., Wilson, K. S., Mangani, S., & Ciurli, S. (2004) · Journal of the American Chemical Society · doi:10.1021/ja049618p · Cited by 172 · see citing works
Structure of dehydroquinate synthase reveals an active site capable of multistep catalysis
Carpenter, E. P., Hawkins, A. R., Frost, J. W., & Brown, K. A. (1998) · Nature · doi:10.1038/28431 · Cited by 144 · see citing works
3 Determinants that govern high-affinity calcium binding
Linse, S. S., & Forsén, S. (1995) · Advances in second messenger and phosphoprotein research · doi:10.1016/s1040-7952(05)80005-9 · Cited by 127 · see citing works
Essen, L., Perišić, O., Katan, M., Wu, Y., Roberts, M. F., & Williams, R. L. (1997) · Biochemistry · doi:10.1021/bi962512p · Cited by 125 · see citing works
Soluble methane monooxygenase: activation of dioxygen and methane
Kopp, D. A., & Lippard, S. J. (2002) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00366-6 · Cited by 117 · see citing works
Dreyer, M., & Schulz, G. E. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0332 · Cited by 111 · see citing works
Snapshots of the Reaction Mechanism of Matrix Metalloproteinases
Bertini, I., Calderone, V., Fragai, M., Luchinat, C., Maletta, M., & Yeo, K. J. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200603100 · Cited by 109 · see citing works
Self-citationJaiswal, J. K. (2001) · Journal of Biosciences · doi:10.1007/bf02703745 · Cited by 104 · see citing works
Product binding and role of the C-terminal region in Class I D-fructose 1, 6-bisphosphate aldolase
Blom, N. S., & SYGUSCH, J. (1997) · Nature Structural & Molecular Biology · doi:10.1038/nsb0197-36 · Cited by 94 · see citing works
Novel active site in Escherichia coli fructose 1,6-bisphosphate aldolase
Blom, N. S., Tétreault, S., Coulombe, R., & SYGUSCH, J. (1996) · Nature Structural & Molecular Biology · doi:10.1038/nsb1096-856 · Cited by 88 · see citing works
Hoke, K. R., Cobb, N. J., Armstrong, F. A., & Hille, R. (2004) · Biochemistry · doi:10.1021/bi0357154 · Cited by 87 · see citing works
Whittaker, M. M., Barynin, V. V., Antonyuk, S. V., & Whittaker, J. W. (1999) · Biochemistry · doi:10.1021/bi990499d · Cited by 85 · see citing works
Chen, G., Edwards, T., D'souz, V. M., & Holz, R. C. (1997) · Biochemistry · doi:10.1021/bi9618676 · Cited by 84 · see citing works
Metals in the “omics” world: copper homeostasis and cytochrome c oxidase assembly in a new light
Bertini, I., & Cavallaro, G. (2007) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-007-0316-9 · Cited by 77 · see citing works
Self-citationZalatan, J. G., Catrina, I. E., Mitchell, R., Grzyska, P. K., O’Brien, P., Herschlag, D., & Hengge, A. C. (2007) · Journal of the American Chemical Society · doi:10.1021/ja072196+ · Cited by 72 · see citing works
Holliday, G. L., Almonacid, D. E., Bartlett, G. J., O’Boyle, N. M., Torrance, J., Murray‐Rust, P., Mitchell, J. B. O., & Thornton, J. M. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl774 · Cited by 70 · see citing works
Self-citationZhou, T., Mo, Y., Liu, A., Zhou, Z., & Tsai, K. R. (2004) · Inorganic Chemistry · doi:10.1021/ic0342301 · Cited by 68 · see citing works
Błaszczyk, J., Shi, G., Honggao Yan, A., & Ji, X. (2000) · Structure · doi:10.1016/s0969-2126(00)00502-5 · Cited by 67 · see citing works
Structural Basis for the Design of Antibiotics Targeting Peptide Deformylase,
Hao, B., Gong, W., Rajagopalan, P. T. R., Zhou, Y., Pei, D., & Chan, M. K. (1999) · Biochemistry · doi:10.1021/bi982594c · Cited by 66 · see citing works
On the mechanism of methyl-coenzyme M reductase
Ermler, U. (2005) · Dalton Transactions · doi:10.1039/b506697b · Cited by 64 · see citing works
Lüthi, D., Günzel, D., & McGuigan, J. A. S. (1999) · Experimental Physiology · doi:10.1017/s0958067099017996 · Cited by 62 · see citing works
Crystal Structure of Methylmalonyl-Coenzyme A Epimerase from P. shermanii
McCarthy, A. A., Baker, H. M., Shewry, S. C., Patchett, M. L., & Baker, E. N. (2001) · Structure · doi:10.1016/s0969-2126(01)00622-0 · Cited by 54 · see citing works
PDBSprotEC: a Web-accessible database linking PDB chains to EC numbers via SwissProt
Martin, A. C. R. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth048 · Cited by 54 · see citing works
Individual Reduction Potentials of the Iron Ions in Fe2S2and High-Potential Fe4S4Ferredoxins
Banci, L., Bertini, I., Savellini, G. G., & Luchinat, C. (1996) · Inorganic Chemistry · doi:10.1021/ic960051q · Cited by 42 · see citing works
Self-citationExplorEnz: a MySQL database of the IUBMB enzyme nomenclature
McDonald, A. G., Boyce, S., Moss, G. P., Dixon, H. B. F., & Tipton, K. F. (2007) · BMC Biochemistry · doi:10.1186/1471-2091-8-14 · Cited by 37 · see citing works
Mowat, C. G., Wehenkel, A. M., Green, A. J., Walkinshaw, M. D., Reid, G. A., & Chapman, S. K. (2004) · Biochemistry · doi:10.1021/bi049263m · Cited by 33 · see citing works
Martin, S. F., & Hergenrother, P. J. (1999) · Biochemistry · doi:10.1021/bi9821216 · Cited by 26 · see citing works
Biological inorganic chemistry
Weller, M. T., Rourke, J. P., Overton, T., & Armstrong, F. A. (2018) · Oxford University Press eBooks · doi:10.1093/hesc/9780198768128.003.0029 · Cited by 12 · see citing works
Li, Y., Błaszczyk, J., Wu, Y., Shi, G., Ji, X., & Honggao Yan, A. (2005) · Biochemistry · doi:10.1021/bi0503495 · Cited by 11 · see citing works
Electron transfer in trimethylamine dehydrogenase and electrontransferring flavoprotein
Scrutton, N. S., Basran, J., Wilson, E. K., Chohan, K. K., Jang, M.-H., Sutcliffe, M. J., & Hille, R. (1999) · Biochemical Society Transactions · doi:10.1042/bst0270196 · Cited by 4 · see citing works
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Fluorescent Sensors for Measuring Metal Ions in Living Systems
Carter, K. P., Young, A. M., & Palmer, A. E. (2014) · Chemical Reviews · doi:10.1021/cr400546e · Cited by 2,443 · see citing works
Nutritional immunity: transition metals at the pathogen–host interface
Hood, M. I., & Skaar, E. P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2836 · Cited by 1,535 · see citing works
Metalloproteins and metal sensing
Waldron, K. J., Rutherford, J. C., Ford, D., & Robinson, N. J. (2009) · Nature · doi:10.1038/nature08300 · Cited by 1,269 · see citing works
Li, P., Roberts, B. P., Chakravorty, D. K., & Merz, K. M. (2013) · Journal of Chemical Theory and Computation · doi:10.1021/ct400146w · Cited by 792 · see citing works
Biomedicine Meets Fenton Chemistry
Tang, Z., Zhao, P., Wang, H., Liu, Y., & Bu, W. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00977 · Cited by 745 · see citing works
Self‐Healing Polymers Based on Coordination Bonds
Li, C., & Zuo, J. (2019) · Advanced Materials · doi:10.1002/adma.201903762 · Cited by 724 · see citing works
Nutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701 · see citing works
Nutritional immunity beyond iron: a role for manganese and zinc
Kehl-Fie, T. E., & Skaar, E. P. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.11.008 · Cited by 634 · see citing works
Witkowska, D., Słowik, J., & Chilicka, K. (2021) · Molecules · doi:10.3390/molecules26196060 · Cited by 623 · see citing works
New roles for bacterial siderophores in metal transport and tolerance
Schalk, I. J., Hannauer, M., & Braud, A. (2011) · Environmental Microbiology · doi:10.1111/j.1462-2920.2011.02556.x · Cited by 583 · see citing works
Palladium-mediated intracellular chemistry
Yusop, M. R., Unciti‐Broceta, A., Johansson, E. M. V., Sanchez-Martin, R. M., & Bradley, M. (2011) · Nature Chemistry · doi:10.1038/nchem.981 · Cited by 534 · see citing works
A Molecular Mechanism for Bacterial Susceptibility to Zinc
McDevitt, C. A., Ogunniyi, A. D., Valkov, E., Lawrence, M. C., Kobe, B., McEwan, A. G., & Paton, J. C. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002357 · Cited by 484 · see citing works
Christensen, A. S., Kubař, T., Cui, Q., & Elstner, M. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00584 · Cited by 446 · see citing works
Taking into Account the Ion-Induced Dipole Interaction in the Nonbonded Model of Ions
Li, P., & Merz, K. M. (2013) · Journal of Chemical Theory and Computation · doi:10.1021/ct400751u · Cited by 437 · see citing works
Kehl-Fie, T. E., Chitayat, S., Hood, M. I., Damo, S., Restrepo, N., Garcia, C., Munro, K. A., Chazin, W. J., & Skaar, E. P. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.07.004 · Cited by 419 · see citing works
Currin, A., Swainston, N., Day, P. J., & Kell, D. B. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00351a · Cited by 383 · see citing works
Damo, S. M., Kehl-Fie, T. E., Sugitani, N., Holt, M. E., Rathi, S., Murphy, W. J., Zhang, Y., Betz, C., Hench, L., Fritz, G., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220341110 · Cited by 388 · see citing works
Metal Preferences and Metallation
Foster, A. W., Osman, D., & Robinson, N. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.588145 · Cited by 381 · see citing works
Metallomics: the concept and methodology
Mounicou, S., Szpunar, J., & Łobiński, R. (2009) · Chemical Society Reviews · doi:10.1039/b713633c · Cited by 371 · see citing works
Metalloproteomes: A Bioinformatic Approach
Andreini, C., Bertini, I., & Rosato, A. (2009) · Accounts of Chemical Research · doi:10.1021/ar900015x · Cited by 370 · see citing works
Self-citationKell, D. B. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0577-x · Cited by 361 · see citing works
History of biological metal utilization inferred through phylogenomic analysis of protein structures
Dupont, C. L., Butcher, A., Valas, R. E., Bourne, P. E., & Caetano-Anollés, G. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912491107 · Cited by 331 · see citing works
Broadening the Scope of Biocatalysis in Sustainable Organic Synthesis
Sheldon, R. A., & Brady, D. (2019) · ChemSusChem · doi:10.1002/cssc.201900351 · Cited by 307 · see citing works
The Mechanical Role of Metal Ions in Biogenic Protein‐Based Materials
Degtyar, E., Harrington, M. J., Politi, Y., & Fratzl, P. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201404272 · Cited by 306 · see citing works
Kubillus, M., Kubař, T., Gaus, M., Řezáč, J., & Elstner, M. (2014) · Journal of Chemical Theory and Computation · doi:10.1021/ct5009137 · Cited by 302 · see citing works
Cherrak, A., Mokhtari-Soulimane, N. A., Berroukeche, F., Bensenane, B., Cherbonnel, A., Merzouk, H., & Elhabiri, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165575 · Cited by 303 · see citing works
The Hitchhiker's guide to biocatalysis: recent advances in the use of enzymes in organic synthesis
Sheldon, R. A., Brady, D., & Bode, M. L. (2020) · Chemical Science · doi:10.1039/c9sc05746c · Cited by 300 · see citing works
Harischandra, D. S., Ghaisas, S., Zenitsky, G. D., Jin, H., Kanthasamy, A., Anantharam, V., & Kanthasamy, A. G. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00654 · Cited by 290 · see citing works
Do Iron Oxide Nanoparticles Have Significant Antibacterial Properties?
Gudkov, S. V., Burmistrov, D. E., Serov, D. A., Ребезов, М. Б., Semenova, A., & Lisitsyn, A. B. (2021) · Antibiotics · doi:10.3390/antibiotics10070884 · Cited by 291 · see citing works
The Biochemical Properties of Manganese in Plants
Schmidt, S. B., & Husted, S. (2019) · Plants · doi:10.3390/plants8100381 · Cited by 279 · see citing works
Targeting Metalloenzymes for Therapeutic Intervention
Chen, A. Y., Adamek, R. N., Dick, B. L., Credille, C. V., Morrison, C. N., & Cohen, S. M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00201 · Cited by 275 · see citing works
Regulation of Cation Balance inSaccharomyces cerevisiae
Cyert, M., & Philpott, C. C. (2013) · Genetics · doi:10.1534/genetics.112.147207 · Cited by 253 · see citing works
MetalPDB in 2018: a database of metal sites in biological macromolecular structures
Putignano, V., Rosato, A., Banci, L., & Andreini, C. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx989 · Cited by 251 · see citing works
Self-citationCellular transport and homeostasis of essential and nonessential metals
Martinez‐Finley, E. J., Chakraborty, S., Fretham, S. J. B., & Aschner, M. (2012) · Metallomics · doi:10.1039/c2mt00185c · Cited by 239 · see citing works
A bioinformatics view of zinc enzymes
Andreini, C., & Bertini, I. (2012) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2011.11.020 · Cited by 227 · see citing works
Self-citationMetalPDB: a database of metal sites in biological macromolecular structures
Andreini, C., Cavallaro, G., Lorenzini, S., & Rosato, A. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1063 · Cited by 227 · see citing works
Self-citationPajarillo, E. A. B., Lee, E.-S., & Kang, D. (2021) · Animal nutrition · doi:10.1016/j.aninu.2021.03.005 · Cited by 227 · see citing works
Kehl-Fie, T. E., Zhang, Y., Moore, J. L., Farrand, A. J., Hood, M. I., Rathi, S., Chazin, W. J., Caprioli, R. M., & Skaar, E. P. (2013) · Infection and Immunity · doi:10.1128/iai.00420-13 · Cited by 213 · see citing works
Metal limitation and toxicity at the interface between host and pathogen
Becker, K. W., & Skaar, E. P. (2014) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12087 · Cited by 223 · see citing works
The ins and outs of bacterial iron metabolism
Frawley, E. R., & Fang, F. C. (2014) · Molecular Microbiology · doi:10.1111/mmi.12709 · Cited by 222 · see citing works
The BRENDA enzyme information system–From a database to an expert system
Schomburg, I., Jeske, L., Ulbrich, M., Placzek, S., Chang, A., & Schomburg, D. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.020 · Cited by 222 · see citing works
Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death
Li, Y., Du, Y., Zhou, Y., Chen, Q., Luo, Z., Ren, Y., Chen, X., & Chen, G. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01267-1 · Cited by 220 · see citing works
Akhtar, A. A., & Turner, D. P. J. (2022) · Microbial Pathogenesis · doi:10.1016/j.micpath.2022.105734 · Cited by 206 · see citing works
Li, Z., Song, L. F., Li, P., & Merz, K. M. (2020) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.0c00194 · Cited by 203 · see citing works
Effects of magnesium and related divalent metal ions in topoisomerase structure and function
Sissi, C., & Palumbo, M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp024 · Cited by 195 · see citing works
Parametrization of DFTB3/3OB for Magnesium and Zinc for Chemical and Biological Applications
Lu, X., Gaus, M., Elstner, M., & Cui, Q. (2014) · The Journal of Physical Chemistry B · doi:10.1021/jp506557r · Cited by 192 · see citing works
The Impact of Dietary Transition Metals on Host-Bacterial Interactions
Lopez, C. A., & Skaar, E. P. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.05.008 · Cited by 190 · see citing works
The biological occurrence and trafficking of cobalt
Okamoto, S., & Eltis, L. D. (2011) · Metallomics · doi:10.1039/c1mt00056j · Cited by 187 · see citing works
Kochańczyk, T., Drozd, A., & Krężel, A. (2014) · Metallomics · doi:10.1039/c4mt00094c · Cited by 185 · see citing works
Visualizing Group II Intron Catalysis through the Stages of Splicing
Marcia, M., & Pyle, A. M. (2012) · Cell · doi:10.1016/j.cell.2012.09.033 · Cited by 176 · see citing works
Whelan, S., Lucey, B., & Finn, K. (2023) · Microorganisms · doi:10.3390/microorganisms11092169 · Cited by 196 · see citing works
Understanding the Functional Roles of Amino Acid Residues in Enzyme Catalysis
Holliday, G. L., Mitchell, J. B. O., & Thornton, J. M. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.05.015 · Cited by 175 · see citing works
Self-citationStappen, C. V., Deng, Y., Liu, Y., Heidari, H., Wang, J., Zhou, Y., Ledray, A. P., & Lu, Y. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00106 · Cited by 174 · see citing works
Trifluoromethyl ketones: properties, preparation, and application
Kelly, C. B., Mercadante, M., & Leadbeater, N. E. (2013) · Chemical Communications · doi:10.1039/c3cc46266h · Cited by 173 · see citing works
Molybdenum enzymes, their maturation and molybdenum cofactor biosynthesis in Escherichia coli
Iobbi‐Nivol, C., & Leimkühler, S. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.11.007 · Cited by 170 · see citing works
Metal–Organic Framework Disintegrants: Enzyme Preparation Platforms with Boosted Activity
An, H., Song, J., Wang, T., Xiao, N., Zhang, Z., Cheng, P., Ma, S., Huang, H., & Chen, Y. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202007827 · Cited by 172 · see citing works
Force Field Independent Metal Parameters Using a Nonbonded Dummy Model
Duarte, F., Bauer, P., Barrozo, A. H., Amrein, B. A., Purg, M., Åqvist, J., & Kamerlin, S. C. L. (2014) · The Journal of Physical Chemistry B · doi:10.1021/jp501737x · Cited by 168 · see citing works
Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas
Hong‐Hermesdorf, A., Miethke, M., Gallaher, S. D., Kropat, J., Dodani, S. C., Chan, J., Barupala, D., Domaille, D. W., Shirasaki, D., Loo, J. A., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1662 · Cited by 165 · see citing works
Lazarenko, V. A., Дороватовский, П. В., Zubavichus, Y. V., Burlov, A. S., Koshchienko, Y. V., Власенко, В. Г., & Khrustalev, V. N. (2017) · Crystals · doi:10.3390/cryst7110325 · Cited by 164 · see citing works
Functions of elements in soil microorganisms
Hemkemeyer, M., Schwalb, S. A., Heinze, S., Joergensen, R. G., & Wichern, F. (2021) · Microbiological Research · doi:10.1016/j.micres.2021.126832 · Cited by 159 · see citing works
A battle for iron: host sequestration and Staphylococcus aureus acquisition
Haley, K. P., & Skaar, E. P. (2012) · Microbes and Infection · doi:10.1016/j.micinf.2011.11.001 · Cited by 157 · see citing works
“The conserved requirement for iron is due to the large number of proteins that utilize the versatile redox potential of this metal [27].”
BackgroundInfluentialGrim, K. P., San Francisco, B., Radin, J. N., Brazel, E. B., Kelliher, J. L., Párraga Solórzano, P. K., Kim, P. C., McDevitt, C. A., & Kehl-Fie, T. E. (2017) · mBio · doi:10.1128/mbio.01281-17 · Cited by 152 · see citing works
Potentiation of hydrogen peroxide toxicity: From catalase inhibition to stable DNA-iron complexes
Mahaseth, T., & Kuzminov, A. (2016) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2016.08.006 · Cited by 151 · see citing works
Remy, L., Carrière, M., Derré‐Bobillot, A., Martini, C., Sanguinetti, M., & Borezée‐Durant, E. (2013) · Molecular Microbiology · doi:10.1111/mmi.12126 · Cited by 139 · see citing works
Beretta, G., Mastorgıo, A. F., Pedrali, L., Saponaro, S., & Sezenna, E. (2019) · Reviews in Environmental Science and Bio/Technology · doi:10.1007/s11157-018-09491-9 · Cited by 148 · see citing works
Metals as phagocyte antimicrobial effectors
Sheldon, J. R., & Skaar, E. P. (2019) · Current Opinion in Immunology · doi:10.1016/j.coi.2019.04.002 · Cited by 143 · see citing works
Zhang, Y., & Gladyshev, V. N. (2009) · Chemical Reviews · doi:10.1021/cr800557s · Cited by 143 · see citing works
Regulation of Rubisco activity in crops
Amaral, J., Lobo, A. K. M., & Carmo‐Silva, E. (2023) · New Phytologist · doi:10.1111/nph.19369 · Cited by 143 · see citing works
Bacterial Metabolism Shapes the Host–Pathogen Interface
Passalacqua, K. D., Charbonneau, M., & O’Riordan, M. X. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.vmbf-0027-2015 · Cited by 143 · see citing works
Xu, G., Cheng, C., Yuan, W., Liu, Z., Zhu, L., Li, X., Lu, Y., Chen, Z., Liu, J., Cui, Z., et al. (2019) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2019.126743 · Cited by 141 · see citing works
Ion-doped hydroxyapatite: An impasse or the road to follow?
Uskoković, V. (2020) · Ceramics International · doi:10.1016/j.ceramint.2020.02.001 · Cited by 140 · see citing works
ZnuA and zinc homeostasis in Pseudomonas aeruginosa
Pederick, V. G., Eijkelkamp, B. A., Begg, S. L., Ween, M. P., McAllister, L. J., Paton, J. C., & McDevitt, C. A. (2015) · Scientific Reports · doi:10.1038/srep13139 · Cited by 138 · see citing works
Diversity of the metal-transporting P1B-type ATPases
Smith, A. T., Smith, K. P., & Rosenzweig, A. C. (2014) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-014-1129-2 · Cited by 136 · see citing works
Imperfect coordination chemistry facilitates metal ion release in the Psa permease
Couñago, R. M., Ween, M. P., Neville, S. L., Bajaj, M., Zuegg, J., O’Mara, M. L., Cooper, M. A., McEwan, A. G., Paton, J. C., Kobe, B., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1382 · Cited by 137 · see citing works
Minimal Functional Sites Allow a Classification of Zinc Sites in Proteins
Andreini, C., Bertini, I., & Cavallaro, G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026325 · Cited by 136 · see citing works
Self-citationThe Compositional and Evolutionary Logic of Metabolism
Braakman, R., & Smith, E. (2012) · Physical Biology · doi:10.1088/1478-3975/10/1/011001 · Cited by 158 · see citing works
An Artificial Metalloenzyme: Creation of a Designed Copper Binding Site in a Thermostable Protein
Podtetenieff, J., Taglieber, A., Bill, E., Reijerse, E. J., & Reetz, M. T. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201002106 · Cited by 135 · see citing works
Der, B. S., Edwards, D., & Kuhlman, B. A. (2012) · Biochemistry · doi:10.1021/bi201881p · Cited by 134 · see citing works
Site-Selective Conjugation of Native Proteins with DNA
Trads, J. B., Tørring, T., & Gothelf, K. V. (2017) · Accounts of Chemical Research · doi:10.1021/acs.accounts.6b00618 · Cited by 134 · see citing works
Decoding the Evolution of Melanin in Vertebrates
McNamara, M. E., Rossi, V., Slater, T. S., Rogers, C. S., Ducrest, A., Dubey, S., & Roulin, A. (2021) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2020.12.012 · Cited by 127 · see citing works
The role of metal ions in X-ray-induced photochemistry
Stumpf, V., Gokhberg, K., & Cederbaum, L. S. (2016) · Nature Chemistry · doi:10.1038/nchem.2429 · Cited by 130 · see citing works
Eijkelkamp, B. A., Morey, J. R., Ween, M. P., Ong, C. Y., McEwan, A. G., Paton, J. C., & McDevitt, C. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089427 · Cited by 130 · see citing works
Transition metal ions at the crossroads of mucosal immunity and microbial pathogenesis
Diaz-Ochoa, V. E., Jellbauer, S., Klaus, S., & Raffatellu, M. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00002 · Cited by 129 · see citing works
Serum total oxidant/antioxidant status and trace element levels in breast cancer patients
Feng, J., Lu, L. H., Zeng, P., Yang, Y.-H., Luo, J. P., Yang, Y., & Wang, D. (2011) · International Journal of Clinical Oncology · doi:10.1007/s10147-011-0327-y · Cited by 129 · see citing works
Neville, S. L., Eijkelkamp, B. A., Luo, Z., Couñago, R. M., Morey, J. R., Maher, M. J., Ong, C. Y., McEwan, A. G., Kobe, B., O’Mara, M. L., et al. (2015) · Nature Communications · doi:10.1038/ncomms7418 · Cited by 128 · see citing works
Nicotianamine is a major player in plant Zn homeostasis
Clemens, S., Deinlein, U., Ahmadi, H., Höreth, S., & Uraguchi, S. (2013) · BioMetals · doi:10.1007/s10534-013-9643-1 · Cited by 128 · see citing works
Mulkidjanian, A. Y., & Galperin, M. Y. (2009) · Biology Direct · doi:10.1186/1745-6150-4-27 · Cited by 130 · see citing works
Manganese acquisition and homeostasis at the host-pathogen interface
Lisher, J. P., & Giedroc, D. P. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00091 · Cited by 127 · see citing works
Graded expression of zinc-responsive genes through two regulatory zinc-binding sites in Zur
Shin, J.-H., Jung, H. J., An, Y. J., Cho, Y.-B., Cha, S.-S., & Roe, J.-H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017744108 · Cited by 124 · see citing works
Klein, J. S., & Lewinson, O. (2011) · Metallomics · doi:10.1039/c1mt00073j · Cited by 126 · see citing works
Garcia, Y. M., Barwinska‐Sendra, A., Tarrant, E., Skaar, E. P., Waldron, K. J., & Kehl‐Fie, T. E. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006125 · Cited by 124 · see citing works
Yin, X., Ma, K.-Y., Wang, Y.-L., Sun, Y., Shang, X., Zhao, Z.-M., Wang, R.-X., Chen, Y.-J., Zhu, J.-K., & Liu, Y. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c01322 · Cited by 122 · see citing works
Küpper, H., Benedikty, Z., Morina, F., Andresen, E., Mishra, A., & Trtílek, M. (2018) · PLANT PHYSIOLOGY · doi:10.1104/pp.18.00953 · Cited by 121 · see citing works
Miethke, M. (2012) · Metallomics · doi:10.1039/c2mt20193c · Cited by 121 · see citing works
The mechanisms of nickel toxicity in aquatic environments: An adverse outcome pathway analysis
Brix, K. V., Schlekat, C. E., & Garman, E. R. (2016) · Environmental Toxicology and Chemistry · doi:10.1002/etc.3706 · Cited by 115 · see citing works
The role of metal ions in the virulence and viability of bacterial pathogens
Neville, S. L. (2019) · Biochemical Society Transactions · doi:10.1042/bst20180275 · Cited by 114 · see citing works
The role of ATP-binding cassette transporters in bacterial pathogenicity
Lewis, V. G., Ween, M. P., & McDevitt, C. A. (2012) · PROTOPLASMA · doi:10.1007/s00709-011-0360-8 · Cited by 110 · see citing works
Çakmak, İ., Brown, P. H., Colmenero-Flores, J. M., Husted, S., Kutman, B. Y., Nikolić, M., Rengel, Z., Schmidt, S. B., & Zhao, F. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-819773-8.00017-4 · Cited by 115 · see citing works
Competition for zinc binding in the host-pathogen interaction
Cerasi, M., Ammendola, S., & Battistoni, A. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00108 · Cited by 111 · see citing works
Martínez‐Calvo, M., Couceiro, J. R., Destito, P., Rodríguez, J., Mosquera, J., & Mascarenas, J. L. (2018) · ACS Catalysis · doi:10.1021/acscatal.8b01606 · Cited by 111 · see citing works
- Authors
- Andreini, C., Bertini, I., Cavallaro, G., Holliday, G. L., & Thornton, J. M.
- Affiliations
- University of Florence (IT)
- European Bioinformatics Institute (GB)
- Corresponding author
- Thornton, Janet M.
- Venue
- JBIC Journal of Biological Inorganic Chemistry
- Published
- 2008-07-05
- Volume
- 13
- Issue
- 8
- Pages
- 1205-1218
- ISSN
- 0949-8257 (ISSN-L)
- 1432-1327
- OpenAlex
- W2052498582
- Cited by
- 1,150
- References
- 72
- Citations by year
- 2026: 68 · 2025: 92 · 2024: 108 · 2023: 89 · 2022: 92 · 2021: 105 · 2020: 87 · 2019: 80 · 2018: 53 · 2017: 59 · 2016: 62 · 2015: 38 · 2014: 47 · 2013: 44 · 2012: 41
- FWCI
- 16.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- JBIC Journal of Biological Inorganic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- BIROn (Birkbeck, University of London) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- Wellcome Trust (062347)
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Keywords
- metal ions, metalloenzymes, enzyme catalysis, redox-active metal ions, Lewis acid catalysis, magnesium, zinc, calcium, iron, manganese, cobalt, molybdenum, copper, nickel, cofactors
- MeSH terms
- Enzymes, Ions, Magnesium, Manganese, Metalloproteins, Metals, Models, Chemical, Oxidation-Reduction, Oxidoreductases, Transferases, Databases, Protein, Biocatalysis
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