5y6d: Difference between revisions
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==VIM-2 metallo-beta-lactamase in complex with (R)-2-(4-fluorophenyl)-2-((S)-3-mercapto-2-methylpropanamido)acetic acid (compound 11)== | |||
<StructureSection load='5y6d' size='340' side='right'caption='[[5y6d]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5y6d]] is a 4 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=5Y6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y6D 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8PL:(2R)-2-(4-fluorophenyl)-2-[[(2S)-2-methyl-3-sulfanyl-propanoyl]amino]ethanoic+acid'>8PL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=5y6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y6d OCA], [https://pdbe.org/5y6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y6d RCSB], [https://www.ebi.ac.uk/pdbsum/5y6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y6d 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 emergence and global spread of metallo-beta-lactamase (MBL) mediated resistance to almost all beta-lactam antibacterials poses a serious threat to public health. Since no clinically useful MBL inhibitors have been reported, there is an urgent need to develop new potent broad-spectrum MBL inhibitors effective against antibacterial resistance. Herein, we synthesized a set of 2-substituted ((S)-3-mercapto-2-methylpropanamido) acetic acid derivatives, some of which displayed potent inhibition with high ligand efficiency to the clinically relevant MBL subtypes, Verona Integron-encoded MBL (VIM)-2 and New Delhi MBL (NDM)-1. Kinetic studies revealed that the inhibitors are not strong zinc chelators in solution, and they bind reversibly to VIM-2 but dissociate very slowly. Crystallographic analyses revealed that they inhibit VIM-2 via chelating the active site zinc ions and interacting with catalytically important residues. Further cell- and zebrafish-based assays revealed that the inhibitors slightly increase susceptibility of E. coli cells expressing VIM-2 to meropenem, and they have no apparent toxicity to the viability of HEK293T cells and the zebrafish embryogenesis. | |||
((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-beta-lactamase inhibitors: Synthesis, kinetic and crystallographic studies.,Liu S, Jing L, Yu ZJ, Wu C, Zheng Y, Zhang E, Chen Q, Yu Y, Guo L, Wu Y, Li GB Eur J Med Chem. 2018 Feb 10;145:649-660. doi: 10.1016/j.ejmech.2018.01.032. Epub , 2018 Jan 11. PMID:29353720<ref>PMID:29353720</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Li | <div class="pdbe-citations 5y6d" 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: Li G-B]] | |||