View source for 6tmc


==VIM-2_1dh-Triazole inhibitors with promising inhibitor effects against antibiotic resistance metallo-beta-lactamases==
<StructureSection load='6tmc' size='340' side='right'caption='[[6tmc]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6tmc]] is a 1 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=6TMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TMC 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]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NL5:4-[2-(phenylsulfonyl)ethyl]-5-(propan-2-yloxymethyl)-1~{H}-1,2,3-triazole'>NL5</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</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=6tmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tmc OCA], [https://pdbe.org/6tmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tmc RCSB], [https://www.ebi.ac.uk/pdbsum/6tmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tmc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI] 
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== Publication Abstract from PubMed ==
Metallo-beta-lactamases (MBLs) are an emerging cause of bacterial antibiotic resistance by hydrolysing all classes of beta-lactams except monobactams, and the MBLs are not inhibited by clinically available serine-beta-lactamase inhibitors. Two of the most commonly encountered MBLs in clinical isolates worldwide - the New Delhi metallo-beta-lactamase (NDM-1) and the Verona integron-encoded metallo-beta-lactamase (VIM-2) - are included in this study. A series of several NH-1,2,3-triazoles was prepared by a three-step protocol utilizing Banert cascade reaction as the key step. The inhibitor properties were evaluated in biochemical assays against the MBLs VIM-2, NDM-1 and GIM-1, and VIM-2 showed IC50 values down to nanomolar range. High-resolution crystal structures of four inhibitors in complex with VIM-2 revealed hydrogen bonds from the triazole inhibitors to Arg228 and to the backbone of Ala231 or Asn233, along with hydrophobic interactions to Trp87, Phe61 and Tyr67. The inhibitors show reduced MIC in synergy assays with Pseudomonas aeruginosa and Escherichia coli strains harbouring VIM enzymes. The obtained results will be useful for further structural guided design of MBL inhibitors.

Structural studies of triazole inhibitors with promising inhibitor effects against antibiotic resistance metallo-beta-lactamases.,Muhammad Z, Skagseth S, Boomgaren M, Akhter S, Frohlich C, Ismael A, Christopeit T, Bayer A, Leiros HS Bioorg Med Chem. 2020 Aug 1;28(15):115598. doi: 10.1016/j.bmc.2020.115598. Epub, 2020 Jun 18. PMID:32631568<ref>PMID:32631568</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6tmc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Christopeit T]]
[[Category: Leiros H-KS]]