View source for 4pvo


==Crystal Structure of VIM-2 metallo-beta-lactamase in complex with ML302 and ML302F==
<StructureSection load='4pvo' size='340' side='right'caption='[[4pvo]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pvo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PVO 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]] 1.48&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=S3C:(2Z)-2-SULFANYL-3-(2,3,6-TRICHLOROPHENYL)PROP-2-ENOIC+ACID'>S3C</scene>, <scene name='pdbligand=SVB:N-(4-METHYLPIPERAZIN-1-YL)-2-[(5Z)-4-OXO-2-THIOXO-5-(2,3,6-TRICHLOROBENZYLIDENE)-1,3-THIAZOLIDIN-3-YL]ACETAMIDE'>SVB</scene>, <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=4pvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pvo OCA], [https://pdbe.org/4pvo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pvo RCSB], [https://www.ebi.ac.uk/pdbsum/4pvo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pvo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The use of beta-lactam antibiotics is compromised by resistance, which is provided by beta-lactamases belonging to both metallo (MBL)- and serine (SBL)-beta-lactamase subfamilies. The rhodanines are one of very few compound classes that inhibit penicillin-binding proteins (PBPs), SBLs and, as recently reported, MBLs. Here, we describe crystallographic analyses of the mechanism of inhibition of the clinically relevant VIM-2 MBL by a rhodanine, which reveal that the rhodanine ring undergoes hydrolysis to give a thioenolate. The thioenolate is found to bind via di-zinc chelation, mimicking the binding of intermediates in beta-lactam hydrolysis. Crystallization of VIM-2 in the presence of the intact rhodanine led to observation of a ternary complex of MBL, a thioenolate fragment and rhodanine. The crystallographic observations are supported by kinetic and biophysical studies, including (19)F NMR analyses, which reveal the rhodanine-derived thioenolate to be a potent broad-spectrum MBL inhibitor and a lead structure for the development of new types of clinically useful MBL inhibitors.

Rhodanine hydrolysis leads to potent thioenolate mediated metallo-beta-lactamase inhibition.,Brem J, van Berkel SS, Aik W, Rydzik AM, Avison MB, Pettinati I, Umland KD, Kawamura A, Spencer J, Claridge TD, McDonough MA, Schofield CJ Nat Chem. 2014 Dec;6(12):1084-90. doi: 10.1038/nchem.2110. Epub 2014 Nov 17. PMID:25411887<ref>PMID:25411887</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4pvo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Aik WS]]
[[Category: Brem J]]
[[Category: McDonough MA]]
[[Category: Schofield CJ]]