View source for 5zb7


==CTX-M-64 apoenzyme==
<StructureSection load='5zb7' size='340' side='right'caption='[[5zb7]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zb7]] is a 2 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=5ZB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZB7 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]] 1.63&#8491;</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=5zb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zb7 OCA], [https://pdbe.org/5zb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zb7 RCSB], [https://www.ebi.ac.uk/pdbsum/5zb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zb7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C8CP57_ECOLX C8CP57_ECOLX] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The smart design of beta-lactamase inhibitors allowed us to combat extended-spectrum beta-lactamase (ESBL)-producing organisms for many years without developing resistance to these inhibitors. However, novel resistant variants have emerged recently, and notable examples are the CTX-M-190 and CTX-M-199 variants, which carried a S(130)T amino acid substitution and exhibited resistance to inhibitors such as sulbactam and tazobactam. Using mass spectrometric and crystallographic approaches, this study depicted the mechanisms of inhibitor resistance. Our data showed that CTX-M-64 (S(130)T) did not cause any conformational change or exert any effect on its ability to hydrolyze beta-lactam substrates. However, binding of sulbactam, but not clavulanic acid, to the active site of CTX-M-64 (S(130)T) led to the conformational changes in such active site, which comprised the key residues involved in substrate catalysis, namely, Thr(130), Lys(73), Lys(234), Asn(104), and Asn(132). This conformational change weakened the binding of the sulbactam trans-enamine intermediate (TSL) to the active site and rendered the formation of the inhibitor-enzyme complex, which features a covalent acrylic acid (AKR)-T(130) bond, inefficient, thereby resulting in inhibitor resistance in CTX-M-64 (S(130)T). Understanding the mechanisms of inhibitor resistance provided structural insight for the future development of new inhibitors against inhibitor-resistant beta-lactamases.

Structural Insight into the Mechanism of Inhibitor Resistance in CTX-M-199, a CTX-M-64 Variant Carrying the S(130)T Substitution.,Cheng Q, Xu C, Chai J, Zhang R, Wai Chi Chan E, Chen S ACS Infect Dis. 2020 Apr 10;6(4):577-587. doi: 10.1021/acsinfecdis.9b00345. Epub , 2019 Nov 21. PMID:31709791<ref>PMID:31709791</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5zb7" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Chen S]]
[[Category: Cheng Q]]