Cited by 426Enzyme Structure and FunctionProtein Structure and DynamicsCrystal structures of chemical compounds

The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.

Analysis of zinc binding sites in protein crystal structures

Open access

Alberts, Ian L., Nadassy, Katalin, Wodak, Shoshana J.·1998·Protein Science

DOI 10.1002/pro.5560070805PMC PMC2144076

Open this paper in CoChat — free account Open PDF

Abstract

The geometrical properties of zinc binding sites in a dataset of high quality protein crystal structures deposited in the Protein Data Bank have been examined to identify important differences between zinc sites that are directly involved in catalysis and those that play a structural role. Coordination angles in the zinc primary coordination sphere are compared with ideal values for each coordination geometry, and zinc coordination distances are compared with those in small zinc complexes from the Cambridge Structural Database as a guide of expected trends. We find that distances and angles in the primary coordination sphere are in general close to the expected (or ideal) values. Deviations occur primarily for oxygen coordinating atoms and are found to be mainly due to H‐bonding of the oxygen coordinating ligand to protein residues, bidentate binding arrangements, and multi‐zinc sites. We find that H‐bonding of oxygen containing residues (or water) to zinc bound histidines is almost universal in our dataset and defines the elec‐His‐Zn motif. Analysis of the stereochemistry shows that carboxyl elec‐His‐Zn motifs are geometrically rigid, while water elec‐His‐Zn motifs show the most geometrical variation. As catalytic motifs have a higher proportion of carboxyl elec atoms than structural motifs, they provide a more rigid framework for zinc binding. This is understood biologically, as a small distortion in the zinc position in an enzyme can have serious consequences on the enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and residues that provide elecs, and identify conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site. A zinc binding template in protein crystal structures is derived from these observations.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1002/pro.5560070805

Cites

94 of 94 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Advanced inorganic chemistry
(1999) · Choice Reviews Online · doi:10.5860/choice.37-0940 · Cited by 14,314
The protein data bank: A computer-based archival file for macromolecular structures
Bernstein, F. C., Koetzle, T. F., Williams, G. J. B., Meyer, E. F., Brice, M. D., Rodgers, J. R., Kennard, O., Shimanouchi, T., & Tasumi, M. (1977) · Journal of Molecular Biology · doi:10.1016/s0022-2836(77)80200-3 · Cited by 8,574
SCOP: A structural classification of proteins database for the investigation of sequences and structures
Murzin, A. G., Brenner, S. E., Hubbard, T., & Chothia, C. (1995) · Journal of Molecular Biology · doi:10.1016/s0022-2836(05)80134-2 · Cited by 6,445
The Galvanization of Biology: A Growing Appreciation for the Roles of Zinc
Berg, J. M., & Shi, Y. (1996) · Science · doi:10.1126/science.271.5252.1081 · Cited by 1,930
The PROSITE database, its status in 1995
Bairoch, A., Bücher, P., & Hofmann, K. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.1.189 · Cited by 1,916
Zinc coordination, function, and structure of zinc enzymes and other proteins
Vallée, B. L., & Auld, D. S. (1990) · Biochemistry · doi:10.1021/bi00476a001 · Cited by 1,784
Recent Advances in Zinc Enzymology
Lipscomb, W. N., & Sträter, N. (1996) · Chemical Reviews · doi:10.1021/cr950042j · Cited by 1,367
The Cambridge Crystallographic Data Centre: computer-based search, retrieval, analysis and display of information
Allen, F. H., Bellard, S., Brice, M. D., Cartwright, B. A., Doubleday, A., Higgs, H., Hummelink, T., Hummelink-Peters, B. G., Kennard, O., MOTHERWELL, W. D. S., et al. (1979) · Acta Crystallographica Section B · doi:10.1107/s0567740879009249 · Cited by 1,167
ZINC PROTEINS: Enzymes, Storage Proteins, Transcription Factors, and Replication Proteins
Coleman, J. E. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.004341 · Cited by 980
Determination and analysis of the 2 Å structure of copper, zinc superoxide dismutase
Tainer, J. A., Getzoff, E. D., Beem, K. M., Richardson, J. S., & Richardson, D. C. (1982) · Journal of Molecular Biology · doi:10.1016/0022-2836(82)90174-7 · Cited by 953

Show all 93 references

Research works printed but not linked: 5

10.1093/nar/25.1.217 · DOI
Berry MB, 1997, Crystal structures of Bacillus stearothermophilus adenylate kinase with bound Ap 5 A reveals an intermediate lid position and a fully coordinated Mg‐2, Biophys J, 72
Eriksson AE, 1986, Progress in inorganic biochemistry and biophysics, 317
10.1111/j.1432-1033.1995.0830m.x · DOI
WallaceA.1996.The role of His in metal binding sites. Chapter 7 [PhD thesis]. London UK: University College London.

Sorted by citations

Synthetic Analogues Relevant to the Structure and Function of Zinc Enzymes
Parkin, G. (2004) · Chemical Reviews · doi:10.1021/cr0206263 · Cited by 944
Structural classification of zinc fingers: SURVEY AND SUMMARY
Krishna, S. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg161 · Cited by 942
A cryptic protease couples deubiquitination and degradation by the proteasome
Yao, T., & Cohen, R. E. (2002) · Nature · doi:10.1038/nature01071 · Cited by 727
“Rather, the identities of the critical residues suggest that Rpn11 is a Zn 2p -dependent metalloproteas”
Background
Alzheimer's Disease Amyloid-β Binds Copper and Zinc to Generate an Allosterically Ordered Membrane-penetrating Structure Containing Superoxide Dismutase-like Subunits
Curtain, C. C., Ali, F. E. A., Volitakis, I., Cherny, R. A., Norton, R. S., Beyreuther, K. T., Barrow, C. J., Masters, C. L., Bush, A. I., & Barnham, K. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100175200 · Cited by 658
AlphaFill: enriching AlphaFold models with ligands and cofactors
Hekkelman, M. L., de Vries, I., Joosten, R. P., & Perrakis, A. (2023) · Nature Methods · doi:10.1038/s41592-022-01685-y · Cited by 511
“Typically, it is involved in catalysis or in maintaining structural integrity 19 .”
Background
Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase
Tellinghuisen, T. L., Marcotrigiano, J., & Rice, C. M. (2005) · Nature · doi:10.1038/nature03580 · Cited by 518
Principles Governing Mg, Ca, and Zn Binding and Selectivity in Proteins
Dudev, T., & Lim, C. (2003) · Chemical Reviews · doi:10.1021/cr020467n · Cited by 467
Protein Design: Toward Functional Metalloenzymes
Yu, F., Cangelosi, V. M., Zastrow, M. L., Tegoni, M., Plegaria, J. S., Tebo, A. G., Mocny, C. S., Ruckthong, L., Qayyum, H., & Pecoraro, V. L. (2014) · Chemical Reviews · doi:10.1021/cr400458x · Cited by 449
The Function of Zinc Metallothionein: A Link between Cellular Zinc and Redox State
Maret, W. (2000) · Journal of Nutrition · doi:10.1093/jn/130.5.1455s · Cited by 417
Allosteric modulators of NR2B‐containing NMDA receptors: molecular mechanisms and therapeutic potential
Mony, L., Kew, J. N. C., Gunthorpe, M. J., & Paoletti, P. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00304.x · Cited by 420
“, 2005), and bearing side chains commonly found in zinc-binding sites (Alberts et al., 1998).”
Background
The NS5A Protein of Hepatitis C Virus Is a Zinc Metalloprotein
Tellinghuisen, T. L., Marcotrigiano, J., Gorbalenya, A. E., & Rice, C. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407787200 · Cited by 356
Differential Metal Selectivity and Gene Expression of Two Zinc Transporters from Rice
Ramesh, S. A., Shin, R., Eide, D. J., & Schachtman, D. P. (2003) · PLANT PHYSIOLOGY · doi:10.1104/pp.103.026815 · Cited by 350
AutoDock4Zn: An Improved AutoDock Force Field for Small-Molecule Docking to Zinc Metalloproteins
Santos-Martins, D., Forli, S., Ramos, M. J., & Olson, A. J. (2014) · Journal of Chemical Information and Modeling · doi:10.1021/ci500209e · Cited by 318
Zinc Coordination Spheres in Protein Structures
Laitaoja, M., Valjakka, J., & Jänis, J. (2013) · Inorganic Chemistry · doi:10.1021/ic401072d · Cited by 263
Role of Zinc in Human Islet Amyloid Polypeptide Aggregation
Brender, J., Hartman, K. L., Nanga, R. P. R., Popovych, N., de la Salud‐Bea, R., Vivekanandan, S., Marsh, E. N. G., & Ramamoorthy, A. (2010) · Journal of the American Chemical Society · doi:10.1021/ja1007867 · Cited by 238
1.68-Å Crystal Structure of Endopolygalacturonase II fromAspergillus niger and Identification of Active Site Residues by Site-directed Mutagenesis
van Santen, Y., BENEN, J. A. E., Schröter, K.-H., Kalk, K. H., Armand, S., Visser, J., & Dijkstra, B. W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.43.30474 · Cited by 240
Tetrahedral vs Octahedral Zinc Complexes with Ligands of Biological Interest: A DFT/CDM Study
Dudev, T., & Lim, C. (2000) · Journal of the American Chemical Society · doi:10.1021/ja0010296 · Cited by 232
Structure of Golgi α‐mannosidase II: a target for inhibition of growth and metastasis of cancer cells
van den Elsen, J. M. H., Kuntz, D. A., & Rose, D. R. (2001) · The EMBO Journal · doi:10.1093/emboj/20.12.3008 · Cited by 221
Structural Basis of Ubiquitin Recognition by the Deubiquitinating Protease USP2
Renatus, M., Gil-Parrado, S., D'Arcy, A., Eidhoff, U., Gerhartz, B., Hassiepen, U., Pierrat, B., Riedl, R., Vinzenz, D., Worpenberg, S., et al. (2006) · Structure · doi:10.1016/j.str.2006.06.012 · Cited by 217
“(Alberts et al., 1998).”
Zinc and mechanical prowess in the jaws of Nereis , a marine worm
Lichtenegger, H. C., Schöberl, T., Ruokolainen, J., Cross, J. O., Heald, S. M., Birkedal, H., Waite, J. H., & Stucky, G. D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1632658100 · Cited by 214
LAG3 associates with TCR–CD3 complexes and suppresses signaling by driving co-receptor–Lck dissociation
Guy, C. S., Mitrea, D. M., Chou, P.-C., Temirov, J. P., Vignali, K. M., Liu, X., Zhang, H., Kriwacki, R. W., Bruchez, M. P., Watkins, S. C., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01176-4 · Cited by 214
First−Second Shell Interactions in Metal Binding Sites in Proteins: A PDB Survey and DFT/CDM Calculations
Dudev, T., Lin, Dudev, M., & Lim, C. (2003) · Journal of the American Chemical Society · doi:10.1021/ja0209722 · Cited by 205
Structures and Analysis of Highly Homologous Psychrophilic, Mesophilic, and Thermophilic Adenylate Kinases
Bae, E., & Phillips, G. N. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401865200 · Cited by 196
Crystal Structure of a Thermophilic Cytochrome P450 from the Archaeon Sulfolobus solfataricus
Yano, J. K., Koo, L. S., Schuller, D. J., Li, H., de Montellano, P. R. O., & Poulos, T. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004281200 · Cited by 191
Three Dimensional Structure of the MqsR:MqsA Complex: A Novel TA Pair Comprised of a Toxin Homologous to RelE and an Antitoxin with Unique Properties
Brown, B. L., Grigoriu, S., Kim, Y., Arruda, J. M., Davenport, A., Wood, T. K., Peti, W., & Page, R. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000706 · Cited by 190
“The zinc, which serves a structural and not catalytic role [41,42], is coordinated by four cysteines (Cys3, Cys6, Cys37, Cys40) with an average sulfur-zinc distance of 2.”
Background
Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue
Cameron, A. D., Ridderström, M., Olin, B., & Mannervik, B. (1999) · Structure · doi:10.1016/s0969-2126(99)80174-9 · Cited by 184
“higher coordination number when present in catalytic sites [24], particularly when part of a zinc cluster [25]; for example, both leucine aminopeptidase [26] and purple acid phosphatase [27] contain an octahedrally coordinated zinc ion as part of a binuclear metal cluster.”
Background
Zinc hydrolases: the mechanisms of zinc-dependent deacetylases
Hernick, M., & Fierke, C. A. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.08.006 · Cited by 178
A Zinc-binding Region in Vif Binds Cul5 and Determines Cullin Selection
Mehle, A., Thomas, E. R., Rajendran, K. S., & Gabuzda, D. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602413200 · Cited by 180
Metalloregulatory proteins: Metal selectivity and allosteric switching
Reyes-Caballero, H., Campanello, G. C., & Giedroc, D. P. (2011) · Biophysical Chemistry · doi:10.1016/j.bpc.2011.03.010 · Cited by 173
New perspectives of zinc coordination environments in proteins
Maret, W. (2011) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2011.11.018 · Cited by 170
Atomic Proximity between S4 Segment and Pore Domain in Shaker Potassium Channels
Lainé, M., Lin, M., Bannister, J. P., Silverman, W. R., Mock, A. F., Roux, B., & Papazian, D. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00468-9 · Cited by 165
Coordination and catalysis of Zn 2+ in epoxy-based vitrimers
Demongeot, A., Mougnier, S., Okada, S., Soulié‐Ziakovic, C., & Tournilhac, F. (2016) · Polymer Chemistry · doi:10.1039/c6py00752j · Cited by 168
Treponema pallidum TroA is a periplasmic zinc-binding protein with a helical backbone.
Hasemann, C. A., Lee, Y.-H., Deka, R. K., Norgard, M. V., & Radolf, J. D. (1999) · Nature Structural Biology · doi:10.1038/10677 · Cited by 164
Vimentin filament organization and stress sensing depend on its single cysteine residue and zinc binding
Pérez‐Sala, D., Oeste, C. L., Martínez, A. E., Carrasco, M., Garzón, B. S., & Cañada, F. J. (2015) · Nature Communications · doi:10.1038/ncomms8287 · Cited by 162
Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels.
Choe, S., Bixby, K. A., Nanao, M., Shen, N. V., Kreusch, A., Bellamy, H. D., & Pfaffinger, P. J. (1999) · Nature Structural Biology · doi:10.1038/4911 · Cited by 158
Structural Insights into the Protein Splicing Mechanism of PI-SceI
Poland, B. W., Xu, M., & Quiocho, F. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.22.16408 · Cited by 154
Generation of an activating Zn 2+ switch in the dopamine transporter: Mutation of an intracellular tyrosine constitutively alters the conformational equilibrium of the transport cycle
Loland, C. J., Nørregaard, L., Litman, T., & Gether, U. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032386299 · Cited by 151
Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase
Sankaranarayanan, R., Dock‐Brégeon, A., Rees, B., Bovée, M., Caillet, J., Romby, P., Francklyn, C. S., & Moras, D. (2000) · Nature Structural Biology · doi:10.1038/75856 · Cited by 149
The Carboxylate Shift in Zinc Enzymes: A Computational Study
Sousa, S. F., Fernandes, P. A., & Ramos, M. J. (2007) · Journal of the American Chemical Society · doi:10.1021/ja067103n · Cited by 147
Zn Protein Simulations Including Charge Transfer and Local Polarization Effects
Sakharov, D. V., & Lim, C. (2005) · Journal of the American Chemical Society · doi:10.1021/ja0429115 · Cited by 147
A Conserved Structural Module Regulates Transcriptional Responses to Diverse Stress Signals in Bacteria
Campbell, E. A., Greenwell, R. S., Anthony, J. R., Wang, S., Lim, L., Das, K., Sofia, H. J., Donohue, T. J., & Darst, S. A. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.009 · Cited by 145
“Catalytic Zn2+ ions tend to be coordinated by His, Asp, and Glu (the ChrR-CLD Zn2+ has 3His and 1Glu ligands), whereas structural Zn2+ ions are prefer- entially coordinated by Cys (Alberts et al., 1998).”
BackgroundInfluential
Vanadium–phosphatase complexes: Phosphatase inhibitors favor the trigonal bipyramidal transition state geometries
McLauchlan, C. C., Peters, B., Willsky, G. R., & Crans, D. C. (2015) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2014.12.012 · Cited by 141
Factors Governing Metal−Ligand Distances and Coordination Geometries of Metal Complexes
Kuppuraj, G., Dudev, M., & Lim, C. (2009) · The Journal of Physical Chemistry B · doi:10.1021/jp807972e · Cited by 149
Factors Governing the Metal Coordination Number in Metal Complexes from Cambridge Structural Database Analyses
Dudev, M., Wang, J., Dudev, T., & Lim, C. (2006) · The Journal of Physical Chemistry B · doi:10.1021/jp054975n · Cited by 141
Monodentate versus Bidentate Carboxylate Binding in Magnesium and Calcium Proteins: What Are the Basic Principles?
Dudev, T., & Lim, C. (2004) · The Journal of Physical Chemistry B · doi:10.1021/jp0310347 · Cited by 140
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 146
Parallel molecular mechanisms for enzyme temperature adaptation
Pinney, M. M., Mokhtari, D. A., Akiva, E., Yabukarski, F., Sanchez, D. M., Liang, R., Doukov, T. I., Martı́nez, T. J., Babbitt, P. C., & Herschlag, D. (2021) · Science · doi:10.1126/science.aay2784 · Cited by 134
“Consistent with this model, Cys ligands are more common at structural relative to catalytic Zn binding sites (46, 47).”
Influential
Crystal Structure of a Superantigen Bound to the High-Affinity, Zinc-Dependent Site on MHC Class II
Li, Y., Li, H., Dimasi, N., McCormick, J. K., Martinꝉ, R., Schuck, P., Schlievert, P. M., & Mariuzza, R. A. (2001) · Immunity · doi:10.1016/s1074-7613(01)00092-9 · Cited by 135
Zinc-binding structure of a catalytic amyloid from solid-state NMR
Lee, M., Wang, T., Makhlynets, O. V., Wu, Y., Polizzi, N. F., Wu, H., Gosavi, P. M., Stöhr, J., Korendovych, I. V., DeGrado, W. F., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1706179114 · Cited by 133
Treble clef finger--a functionally diverse zinc-binding structural motif
Grishin, N. V. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.8.1703 · Cited by 131
“Zinc is particularly important and is used for diverse functions, from catalytic to structural ( 1 ).”
Background
Carboxylate Binding Modes in Zinc Proteins: A Theoretical Study
Ryde, U. (1999) · Biophysical Journal · doi:10.1016/s0006-3495(99)77110-9 · Cited by 127
“Altogether, this explains why both bidentate and monodentate structures are common among zinc proteins (;30% of the Zn-carboxylate proteins are bidentate (Alberts et al., 1998), whereas among smaller zinc complexes,;10% are bidentate (Carrell et al., 1988)).”
BackgroundInfluential
The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut‐off of host‐cell protein synthesis
Petersen, J. F. W., Cherney, M. M., Liebig, H., Skern, T., Kuechler, E., & James, M. N. G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.20.5463 · Cited by 129
“(Alberts et al., 1998).”
BackgroundInfluential
Physical Basis of Structural and Catalytic Zn-Binding Sites in Proteins
Lee, Y., & Lim, C. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.04.004 · Cited by 124
Analysis of the structural consensus of the zinc coordination centers of metalloprotein structures
Patel, K., Kumar, A., & Durani, S. (2007) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.07.010 · Cited by 123
“The O–Zn–O angles are on the higher side for Eq–Zn–Ax when the bidentate arrangements are excluded, in accordance with the earlier reported observation [18].”
Result
The crystal structure of SdsA1, an alkylsulfatase from Pseudomonas aeruginosa , defines a third class of sulfatases
Hagelueken, G., Adams, T., Wiehlmann, L., Widow, U., Kolmar, H., Tümmler, B., Heinz, D. W., & Schubert, W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510501103 · Cited by 122
Structure of the LpxC deacetylase with a bound substrate-analog inhibitor
Coggins, B. E., Li, X., McClerren, A. L., Hindsgaul, O., Raetz, C. R. H., & Zhou, P. (2003) · Nature Structural & Molecular Biology · doi:10.1038/nsb948 · Cited by 122
Latent LytM at 1.3Å Resolution
Odintsov, S. G., Sabała, I., Marcyjaniak, M., & Bochtler, M. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.11.009 · Cited by 119
“This common, so-called elec-His-Zn motif orients the imidazole ring in space and is believed to make it more basic and thus a better ligand to the metal.(16) In H210, the imidazole N(1) coordinates the Zn2þ, and the N donates a hydrogen bond to the carbonyl oxygen of P200.”
Background
Prediction of transition metal‐binding sites from apo protein structures
Babor, M., Gerzon, S., Raveh, B., Sobolev, V. M., & Edelman, M. (2007) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21587 · Cited by 119
Molecular basis of Pirh2-mediated p53 ubiquitylation
Sheng, Y., Laister, R. C., Lemak, A. S., Wu, B., Tai, E., Duan, S., Lukin, J. A., Sunnerhagen, M., Srisailam, S., Karra, M., et al. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1521 · Cited by 123
“These nonexperimental distance restraints were developed based on analysis of the geometrical properties of zinc binding sites observed in a dataset of high-quality protein crystal structure”
Method
DNA apurinic-apyrimidinic site binding and excision by endonuclease IV
Garcin, E. D., Hosfield, D. J., Desai, S. A., Haas, B. J., Bjørås, M., Cunningham, R. P., & Tainer, J. A. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1414 · Cited by 114
“Notably, our E261Q Endo IV–AP DNA structure reveals that the Zn 3 coordination sphere is incomplet”
Background
DNA binding and cleavage by the periplasmic nuclease Vvn: a novel structure with a known active site
Li, C., Hor, L., Chang, Z.-F., Tsai, L., Yang, W., & Yuan, H. S. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg377 · Cited by 114
Metal-Mediated Affinity and Orientation Specificity in a Computationally Designed Protein Homodimer
Der, B. S., Machius, M., Miley, M. J., Mills, J., Szyperski, T., & Kuhlman, B. A. (2011) · Journal of the American Chemical Society · doi:10.1021/ja208015j · Cited by 112
Docking studies of matrix metalloproteinase inhibitors: zinc parameter optimization to improve the binding free energy prediction
Hu, X., & Shelver, W. H. (2003) · Journal of Molecular Graphics and Modelling · doi:10.1016/s1093-3263(03)00153-0 · Cited by 112
The Structure of the Neisserial Lipooligosaccharide Phosphoethanolamine Transferase A (LptA) Required for Resistance to Polymyxin
Wanty, C., Anandan, A., Piek, S., Walshe, J. L., Ganguly, J., Carlson, R. W., Stubbs, K. A., Kahler, C. M., & Vrielink, A. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.06.029 · Cited by 110
Metal Selectivity Determinants in a Family of Transition Metal Transporters
Podar, D., Scherer, J., Noordally, Z. B., Herzyk, P., Nies, D. H., & Sanders, D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.305649 · Cited by 110
“zinc proteases) (1, 2) or in substrate coordination (e.”
Background
Determination of the binding sites of the proton transfer inhibitors Cd 2+ and Zn 2+ in bacterial reaction centers
Axelrod, H. L., Abresch, E. C., Paddock, M. L., Okamura, M. Y., & Fehér, G. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1542 · Cited by 110
Zinc inhibition of monomeric and dimeric proton channels suggests cooperative gating
Musset, B., Smith, S. M. E., Rajan, S., Cherny, V. V., Sujai, S., Morgan, D., & DeCoursey, T. E. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.188318 · Cited by 109
“4 Å between Zn2+ and its coordinating atom (Alberts et al. 1998).”
BackgroundInfluential
Zinc(II) Binding Site to the Amyloid-β Peptide: Insights from Spectroscopic Studies with a Wide Series of Modified Peptides
Aliès, B., Conte‐Daban, A., Sayen, S., Collin, F., Kieffer, I., Guillon, E., Faller, P., & Hureau, C. (2016) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.6b01733 · Cited by 108
“42,60 We cannot (completely) exclude that a water molecule is the fourth ligand, because e ﬀ ects on Asp1, Glu3, and Asp7 upon Zn(II) binding observed by NMR and XANES could be explained via H-bonding of these residues with the coordinating water.”
Unexpected Deacetylation Mechanism Suggested by a Density Functional Theory QM/MM Study of Histone-Deacetylase-Like Protein
Corminbœuf, C., Hu, P., Tuckerman, M. E., & Zhang, Y. (2006) · Journal of the American Chemical Society · doi:10.1021/ja0600882 · Cited by 108
Defining Proximity Relationships in the Tertiary Structure of the Dopamine Transporter
Loland, C. J., Nørregaard, L., & Gether, U. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.52.36928 · Cited by 107
A General Strategy for the NMR Observation of Half-Integer Quadrupolar Nuclei in Dilute Environments
Lipton, A. S., Sears, J. A., & Ellis, P. D. (2001) · Journal of Magnetic Resonance · doi:10.1006/jmre.2001.2353 · Cited by 107
Inhibition of Metalloprotease Botulinum Serotype A from a Pseudo-peptide Binding Mode to a Small Molecule That Is Active in Primary Neurons
Burnett, J. C., Ruthel, G. T., Stegmann, C. M., Panchal, R. G., Nguyen, T. L., Hermone, A. R., Stafford, R. G., Lane, D. J., Kenny, T., McGrath, C. F., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608166200 · Cited by 106
Crystal structures of an archaeal oligosaccharyltransferase provide insights into the catalytic cycle of N-linked protein glycosylation
Matsumoto, S., Shimada, A., Nyirenda, J., Igura, M., Kawano, Y., & Kohda, D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309777110 · Cited by 105
“Although zinc ions are usually four-coordinated in many metalloenzymes and zincfinger proteins (26), the six-coordination of the zinc ion is consistent with the fact that the six-coordinated Mg ion is reportedly a natural cofactor of OST (27).”
Background
Crystal Structures of an Intein from the Split dnaE Gene of Synechocystis sp. PCC6803 Reveal the Catalytic Model Without the Penultimate Histidine and the Mechanism of Zinc Ion Inhibition of Protein Splicing
Sun, P., Ye, S., Ferrandon, S., Evans, T. C., Xu, M., & Rao, Z. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.09.039 · Cited by 103
“Zinc is coordinated in a T4 (tetrahedral) geometry by four residues, His48, Asp140, His110 (from a neighboring molecule) and the highly conserved residue Cys160 (Figure 4(a)).(34) The metal–donor atom target distances are all within accepted constraints.”
The crystal structure of NS5A domain 1 from genotype 1a reveals new clues to the mechanism of action for dimeric HCV inhibitors
Lambert, S., Langley, D. R., Garnett, J. A., Angell, R. M., Hedgethorne, K., Meanwell, N. A., & Matthews, S. (2014) · Protein Science · doi:10.1002/pro.2456 · Cited by 100
“13 Å) for catalytic metal zinc-coordination sites.(35) The arrangement and proximity of residues Cys 142 and Cys 190 in our model and the presence of electron density in between the residues suggests the formation of a disulphide bridge, despite the presence of DTT in the crystallization buffer, with a distance betwee…”
Background
Engineered Proteins: Redox Properties and Their Applications
Prabhulkar, S., Tian, H. Q., Wang, X., Zhu, J., & Li, C.-Z. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4001 · Cited by 97
“In catalytic sites, the zinc ion is usually exposed and bound to a solvent molecule (2).”
Background
MSDsite: A database search and retrieval system for the analysis and viewing of bound ligands and active sites
Golovin, A., Dimitropoulos, D., Oldfield, T. J., Rachedi, A., & Henrick, K. (2004) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20288 · Cited by 98
“26”
Calculation and Prediction of Binding Free Energies for the Matrix Metalloproteinases
Donini, O., & Kollman, P. A. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm000040d · Cited by 95
Structure-Based Dissection of the Active Site Chemistry of Leukotriene A4 Hydrolase: Implications for M1 Aminopeptidases and Inhibitor Design
Tholander, F., Muroya, A., Roques, B. P., Fournié‐Zaluski, M., Thunnissen, M. M. G. M., & Haeggström, J. Z. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2008.07.018 · Cited by 94
The Active Site of a Zinc-Dependent Metalloproteinase Influences the Computed pKa of Ligands Coordinated to the Catalytic Zinc Ion
Cross, J. B., Duca, J. S., Kaminski, J. J., & Madison, V. (2002) · Journal of the American Chemical Society · doi:10.1021/ja0201810 · Cited by 93
An Intersubunit Zinc Binding Site in Rat P2X2 Receptors
Nagaya, N., Tittle, R. K., Saar, N., Dellal, S. S., & Hume, R. I. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504545200 · Cited by 93
Angiostatin and Endostatin: Endogenous Inhibitors of Tumor Growth
Sim, B. K. L., MacDonald, N. J., & Gubish, E. R. (2000) · Cancer and Metastasis Reviews · doi:10.1023/a:1026551202548 · Cited by 93
“One is that the tetrahedral coordination of the zinc ion by H1, H3, H11, and D76 strongly argues against a catalytic role for the zinc ion where one expects to have a water molecule [44]; secondly and more definitively, Endostatin protein that has the zinc binding ligands deleted and disrupted is still able to inhibit…”
Background
Steric Hindrance Mutagenesis in the Conserved Extracellular Vestibule Impedes Allosteric Binding of Antidepressants to the Serotonin Transporter
Plenge, P., Shi, L., Beuming, T., Te, J. A., Newman, A. H., Weinstein, H., Gether, U., & Loland, C. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.371765 · Cited by 92
“I179H 46 [41;52] 44 [40;48] 32 [29;36] 31 [30;33]”
Structure and dynamics of a primordial catalytic fold generated by in vitro evolution
Chao, F.-A., Morelli, A., Haugner, J., Churchfield, L. A., Hagmann, L. N., Shi, L., Masterson, L. R., Sarangi, R., Veglia, G., & Seelig, B. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1138 · Cited by 92
The Zinc proteome: a tale of stability and functionality
Sousa, S. F., Lopes, A., Fernandes, P. A., & Ramos, M. J. (2009) · Dalton Transactions · doi:10.1039/b904404c · Cited by 94
Robust recognition of zinc binding sites in proteins
Ebert, J. C., & Altman, R. B. (2007) · Protein Science · doi:10.1110/ps.073138508 · Cited by 90
“In addition, although many catalytic zincs are solvent exposed, the side chains of their coordinating residues may nonetheless be buried (Alberts et al. 1998).”
Background
Crystal Structures of Wzb of Escherichia coli and CpsB of Streptococcus pneumoniae, Representatives of Two Families of Tyrosine Phosphatases that Regulate Capsule Assembly
Hagelueken, G., Huang, H., Mainprize, I. L., Whitfield, C., & Naismith, J. H. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.07.026 · Cited by 90
A practical approach to docking of zinc metalloproteinase inhibitors
Hu, X., Baláž, Š., & Shelver, W. H. (2004) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2003.11.002 · Cited by 93
Fluorescence-based biosensing of zinc using carbonic anhydrase
Fierke, C. A., & Thompson, R. B. (2001) · BioMetals · doi:10.1023/a:1012980628412 · Cited by 87
“The preferred geometry of metal ions and the optimum ligand distances have been investigated in both model compounds and in proteins (Alberts & Nadassy 1998; Glusker 1991; Roe & Pang 1999; Rulisek & Vondrasek 1998).”
BackgroundInfluential
Vesicle-associated Membrane Protein (VAMP) Cleavage by a New Metalloprotease from the Brazilian Scorpion Tityus serrulatus
Fletcher, P. L., Fletcher, M. D., Weninger, K., Anderson, T., & Martin, B. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.028365 · Cited by 86
Insights into the Mode of Action of a Putative Zinc Transporter CzrB in Thermus thermophilus
Cherezov, V., Höfer, N., Szebenyi, D. M. E., Kolaj‐Robin, O., Wall, J. G., Gillilan, R. E., Srinivasan, V., Jaroniec, C. P., & Caffrey, M. (2008) · Structure · doi:10.1016/j.str.2008.05.014 · Cited by 86
“The first concerns catalysis; the second structure stabilization (Alberts et al., 1998).”
BackgroundInfluential
ElaC Encodes a Novel Binuclear Zinc Phosphodiesterase
Vogel, A., Schilling, O., Niecke, M., Bettmer, J., & Meyer‐Klaucke, W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112047200 · Cited by 86
Membrane Potential-controlled Inhibition of Cytochromec Oxidase by Zinc
Mills, D. A., Schmidt, B., Hiser, C., Westley, E., & Ferguson-Miller, S. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111922200 · Cited by 86
Comparative analysis of editosome proteins in trypanosomatids
Worthey, E. A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg870 · Cited by 85
“Zinc-centered domains have also been implicated in protein interaction (89).”
Background
Zinc-mediated Allosteric Inhibition of Caspase-6
Velázquez-Delgado, E. M., & Hardy, J. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.397752 · Cited by 84
Tightening of the ATP‐binding sites induces the opening of P2X receptor channels
Jiang, R., Taly, A., Lemoine, D., Martz, A., Cunrath, O., & Grütter, T. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.75 · Cited by 83
“…these histidine residues, and the distance and angle measured between Zn 2 þ and the coordinating atom NE2 of the histidine residues were close to those obtained from the analysis of 111 crystal structures of Zn 2 þ -binding proteins available in the Protein Data Bank (PDB; Alberts et al , 1998).”
Influential
Identification and characterization of zinc-starvation-induced ZIP transporters from barley roots
Pedas, P., Schjoerring, J. K., & Husted, S. (2009) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2009.01.006 · Cited by 83
“For example, several motifs in transcriptional regulatory proteins are stabilized by Zn, including zinc finger domains, which require the binding of Zn for activation of transcription [4].”
Background
Analysis of zinc‐ligand bond lengths in metalloproteins: Trends and patterns
Tamames, B., Sousa, S. F., Tamames, J. A. C., Fernandes, P. A., & Ramos, M. J. (2007) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21536 · Cited by 82
Crystal Structure of Human Riboflavin Kinase Reveals a β Barrel Fold and a Novel Active Site Arch
Karthikeyan, S., Zhou, Q., Mseeh, F., Grishin, N. V., Osterman, A. L., & Zhang, H. (2003) · Structure · doi:10.1016/s0969-2126(03)00024-8 · Cited by 82
A high-field solid-state 35/37Cl NMR and quantum chemical investigation of the chlorine quadrupolar and chemical shift tensors in amino acid hydrochlorides
Chapman, R. P., & Bryce, D. L. (2007) · Physical Chemistry Chemical Physics · doi:10.1039/b712688c · Cited by 80

Authors: Alberts, I. L., Nadassy, K., & Wodak, S. J.
Affiliations: University of Stirling (GB)
European Bioinformatics Institute (GB)
Corresponding author: Wodak, Shoshana J.
ORCID: Alberts, Ian L.
Wodak, Shoshana J.
Venue: Protein Science
Publisher: Wiley
Published: 1998-08
Volume: 7
Issue: 8
Pages: 1700-1716
ISSN: 0961-8368 (ISSN-L)
1469-896X
DOI: 10.1002/pro.5560070805
PMC: PMC2144076
OpenAlex: W2148386309
Cited by: 423
References: 93
Citations by year: 2026: 6 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 11 · 2020: 11 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 18 · 2015: 16 · 2014: 19 · 2013: 11 · 2012: 23
FWCI: 14.55
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3805 d)
Locations: Protein Science (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
Funders: European Bioinformatics Institute
University of Stirling
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Physical Sciences › Chemistry › Inorganic Chemistry › Crystal structures of chemical compounds
Keywords: zinc binding site, zinc coordination geometry, primary coordination sphere, endopeptidase, hydrophobic residues, Protein Data Bank
MeSH terms: Aspartic Acid, Binding Sites, Catalysis, Chlorine, Cysteine, Glutamine, Histidine, Models, Molecular, Molecular Conformation, Nitrogen, Oxygen, Protein Binding, Sulfur, Zinc, Databases, Factual, Crystallography, X-Ray

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Analysis of zinc binding sites in protein crystal structures

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks