View source for 7wzu


==Crystal structure of metallo-beta-lactamase IMP-6.==
<StructureSection load='7wzu' size='340' side='right'caption='[[7wzu]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wzu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WZU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.954&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wzu OCA], [https://pdbe.org/7wzu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wzu RCSB], [https://www.ebi.ac.uk/pdbsum/7wzu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wzu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/K4PWX3_ECOLX K4PWX3_ECOLX] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Gram-negative bacteria producing metallo-beta-lactamases (MBLs) have become a considerable threat to public health. MBLs including the IMP, VIM, and NDM types are Zn(II) enzymes that hydrolyze the beta-lactam ring present in a broad range of antibiotics, such as N-benzylpenicillin, meropenem, and imipenem. Among IMPs, IMP-1 and IMP-6 differ in a single amino acid substitution at position 262, where serine in IMP-1 is replaced by glycine in IMP-6, conferring a change in substrate specificity. To investigate how this mutation influences enzyme function, we examined lactamase inhibition by thiol compounds. Ethyl 3-mercaptopropionate acted as a competitive inhibitor of IMP-1, but a noncompetitive inhibitor of IMP-6. A comparison of the crystal structures previously reported for IMP-1 (PDB code: 5EV6) and IMP-6 (PDB code: 6LVJ) revealed a hydrogen bond between the side chain of Ser262 and Cys221 in IMP-1 but the absence of hydrogen bond in IMP-6, which affects the Zn2 coordination sphere in its active site. We investigated the demetallation rates of IMP-1 and IMP-6 in the presence of chelating agent ethylenediaminetetraacetic acid (EDTA) and found that the demetallation reactions had fast and slow phases with a first-order rate constant (k(fast) = 1.76 h(-1), k(slow) = 0.108 h(-1) for IMP-1, and k(fast) = 14.0 h(-1) and k(slow) = 1.66 h(-1) for IMP-6). The difference in the flexibility of the Zn2 coordination sphere between IMP-1 and IMP-6 may influence the demetallation rate, the catalytic efficiency against beta-lactam antibiotics, and the inhibitory effect of thiol compounds.

Difference in the Inhibitory Effect of Thiol Compounds and Demetallation Rates from the Zn(II) Active Site of Metallo-beta-lactamases (IMP-1 and IMP-6) Associated with a Single Amino Acid Substitution.,Yamaguchi Y, Kato K, Ichimaru Y, Uenosono Y, Tawara S, Ito R, Matsuse N, Wachino JI, Toma-Fukai S, Jin W, Arakawa Y, Otsuka M, Fujita M, Fukuishi N, Sugiura K, Imai M, Kurosaki H ACS Infect Dis. 2023 Jan 13;9(1):65-78. doi: 10.1021/acsinfecdis.2c00395. Epub , 2022 Dec 15. PMID:36519431<ref>PMID:36519431</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wzu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Kurosaki H]]
[[Category: Yamaguchi Y]]