Histidine residues of zinc ligands in β-lactamase II

1. The Zn(II)-requiring beta-lactamase from Bacillus cereus 569/H/9, which has two zinc-binding sites, was examined by 270 MHz 1H n.m.r. spectroscopy. Resonances were assigned to five histidine residues. 2. Resonances attributed to three of the histidine residues in the apoenzyme shift on the addition of one equivalent of Zn(II). 3. Although these three histidine residues are free to titrate in the apoenzyme, none of them titrates over the pH range 6.0–9.0 in the mono-zinc enzyme. 4. The ability of the C-2 protons of these three histidine residues to exchange with solvent (2H2O) is markedly decreased on Zn(II) binding. 5. It is proposed that these three histidine residues act as zinc ligands at the tighter zinc-binding site. 6. Resonances attributed to a fourth histidine residue shift on addition of further zinc to the mono-zinc enzyme. It is proposed that this histidine residue acts as a Zn(II) ligand at the second zinc-binding site.

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Identification of histidine residues that act as zinc ligands in β-lactamase II by differential tritium exchange

Biochemical Journal ◽

10.1042/bj1790459 ◽

1979 ◽

Vol 179 (3) ◽

pp. 459-463 ◽

Cited By ~ 14

Author(s):

G S Baldwin ◽

S G Waley ◽

E P Abraham

Keyword(s):

Bacillus Cereus ◽

Binding Site ◽

Beta Lactamase ◽

Histidine Residues ◽

Tryptic Digest ◽

Beta Lactamase Ii

1. Four histidine-containing peptides have been isolated from a tryptic digest of the Zn2+-requiring beta-lactamase II from Bacillus cereus. One of these peptides probably contains two histidine residues. 2. The presence of one equivalent of Zn2+ substantially decreases the rate of exchange of the C-2 proton in at least two and probably three of the histidine residues of these peptides for solvent 3H. 3. It is concluded that peptides containing at least two of the three histidine residues acting as Zn2+ ligands at the tighter Zn2+-binding site of beta-lactamase II have been identified.

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An altered zinc-binding site confers resistance to a covalent inactivator of New Delhi metallo-beta-lactamase-1 (NDM-1) discovered by high-throughput screening

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2013.03.031 ◽

2013 ◽

Vol 21 (11) ◽

pp. 3138-3146 ◽

Cited By ~ 23

Author(s):

Pei W. Thomas ◽

Timothy Spicer ◽

Michael Cammarata ◽

Jennifer S. Brodbelt ◽

Peter Hodder ◽

...

Keyword(s):

Binding Site ◽

High Throughput ◽

High Throughput Screening ◽

Zinc Binding ◽

New Delhi ◽

Beta Lactamase ◽

Zinc Binding Site

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Prediction of zinc-binding sites using multiple sequence profiles and machine learning methods

Molecular Omics ◽

10.1039/c9mo00043g ◽

2019 ◽

Vol 15 (3) ◽

pp. 205-215 ◽

Cited By ~ 1

Author(s):

Renxiang Yan ◽

Xiaofeng Wang ◽

Yarong Tian ◽

Jing Xu ◽

Xiaoli Xu ◽

...

Keyword(s):

Machine Learning ◽

Binding Site ◽

Binding Sites ◽

Zinc Binding ◽

Biological Mechanisms ◽

Learning Methods ◽

Multiple Sequence ◽

Machine Learning Methods ◽

Zinc Binding Site ◽

Sequence Profiles

The zinc (Zn2+) cofactor has been proven to be involved in numerous biological mechanisms and the zinc-binding site is recognized as one of the most important post-translation modifications in proteins.

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Zincbindpredict—Prediction of Zinc Binding Sites in Proteins

Molecules ◽

10.3390/molecules26040966 ◽

2021 ◽

Vol 26 (4) ◽

pp. 966

Author(s):

Sam M. Ireland ◽

Andrew C. R. Martin

Keyword(s):

Binding Site ◽

Binding Sites ◽

Computational Models ◽

Significant Proportion ◽

Zinc Binding ◽

Web Interface ◽

Zinc Binding Site ◽

Experimental Approaches ◽

Better Than ◽

Novel Protein

Background: Zinc binding proteins make up a significant proportion of the proteomes of most organisms and, within those proteins, zinc performs rôles in catalysis and structure stabilisation. Identifying the ability to bind zinc in a novel protein can offer insights into its functions and the mechanism by which it carries out those functions. Computational means of doing so are faster than spectroscopic means, allowing for searching at much greater speeds and scales, and thereby guiding complimentary experimental approaches. Typically, computational models of zinc binding predict zinc binding for individual residues rather than as a single binding site, and typically do not distinguish between different classes of binding site—missing crucial properties indicative of zinc binding. Methods: Previously, we created ZincBindDB, a continuously updated database of known zinc binding sites, categorised by family (the set of liganding residues). Here, we use this dataset to create ZincBindPredict, a set of machine learning methods to predict the most common zinc binding site families for both structure and sequence. Results: The models all achieve an MCC ≥ 0.88, recall ≥ 0.93 and precision ≥ 0.91 for the structural models (mean MCC = 0.97), while the sequence models have MCC ≥ 0.64, recall ≥ 0.80 and precision ≥ 0.83 (mean MCC = 0.87), with the models for binding sites containing four liganding residues performing much better than this. Conclusions: The predictors outperform competing zinc binding site predictors and are available online via a web interface and a GraphQL API.

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Hydrogen Peroxide Damages the Zinc-Binding Site of Zinc-Deficient Cu,Zn Superoxide Dismutase

Archives of Biochemistry and Biophysics ◽

10.1006/abbi.2001.2418 ◽

2001 ◽

Vol 392 (1) ◽

pp. 8-13 ◽

Cited By ~ 24

Author(s):

Jacinda B. Sampson ◽

Joseph S. Beckman

Keyword(s):

Hydrogen Peroxide ◽

Superoxide Dismutase ◽

Binding Site ◽

Zinc Binding ◽

Zinc Binding Site

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Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1809688116 ◽

2018 ◽

Vol 116 (2) ◽

pp. 528-533 ◽

Cited By ~ 6

Author(s):

Ivan B. Lomakin ◽

Sergey E. Dmitriev ◽

Thomas A. Steitz

Keyword(s):

Crystal Structure ◽

Binding Site ◽

Translation Initiation ◽

Zinc Ion ◽

Zinc Binding ◽

Ion Binding ◽

Binding Interface ◽

Zinc Binding Site ◽

Reading Frames ◽

Zinc Ion Binding

The density-regulated protein (DENR) and the malignant T cell-amplified sequence 1 (MCT-1/MCTS1) oncoprotein support noncanonical translation initiation, promote translation reinitiation on a specific set of mRNAs with short upstream reading frames, and regulate ribosome recycling. DENR and MCT-1 form a heterodimer, which binds to the ribosome. We determined the crystal structure of the heterodimer formed by human MCT-1 and the N-terminal domain of DENR at 2.0-Å resolution. The structure of the heterodimer reveals atomic details of the mechanism of DENR and MCT-1 interaction. Four conserved cysteine residues of DENR (C34, C37, C44, C53) form a classical tetrahedral zinc ion-binding site, which preserves the structure of the DENR’s MCT-1–binding interface that is essential for the dimerization. Substitution of all four cysteines by alanine abolished a heterodimer formation. Our findings elucidate further the mechanism of regulation of DENR-MCT-1 activities in unconventional translation initiation, reinitiation, and recycling.

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2. Zinc Binding Site Motifs as a Means for the Discovery of New Zinc Families

Handbook on Metalloproteins ◽

10.1201/9781482270822-104 ◽

2001 ◽

pp. 951-959

Keyword(s):

Binding Site ◽

Zinc Binding ◽

Zinc Binding Site

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Effect of the hydrogen bond network in carbonic anhydrase II zinc binding site. A theoretical study

Canadian Journal of Chemistry ◽

10.1139/v98-098 ◽

1998 ◽

Vol 76 (7) ◽

pp. 1027-1032 ◽

Cited By ~ 2

Author(s):

Silvia Álvarez-Santos ◽

Àngels González-Lafont ◽

José M Lluch

Keyword(s):

Hydrogen Bond ◽

Carbonic Anhydrase ◽

Binding Site ◽

Zinc Binding ◽

Carbonic Anhydrase Ii ◽

Am1 Method ◽

Hydrogen Bond Network ◽

Zinc Binding Site ◽

Bond Network ◽

Metal Ligand

The hydrogen bond network influence on the carbonic anhydrase II (CAII) zinc binding site has been studied theoretically by using the semiempirical AM1 method. To this aim, quantum mechanical reduced models of wild-type CAII and several CAII variants have been constructed. We have shown that, when a direct metal ligand donates a hydrogen bond to an indirect metal ligand, the first-shell residues enhance their electrostatic interaction with the zinc cation. Thus, the hydrogen-bond network is able to modulate the zinc binding affinity and the zinc-water pKa.Key words: hydrogen bond network, carbonic anhydrase II, Zn2+ metalloenzyme ligands.

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