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==Crystal structure of NDM-1 in complex with D-captopril derivative wss04145== | ==Crystal structure of NDM-1 in complex with D-captopril derivative wss04145== | ||
<StructureSection load='6lj5' size='340' side='right'caption='[[6lj5]]' scene=''> | <StructureSection load='6lj5' size='340' side='right'caption='[[6lj5]], [[Resolution|resolution]] 1.26Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LJ5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6lj5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LJ5 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lj5 OCA], [http://pdbe.org/6lj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lj5 RCSB], [http://www.ebi.ac.uk/pdbsum/6lj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lj5 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EF0:1-[(2S)-2-methyl-3-sulfanyl-propanoyl]piperidine-4-carboxylic+acid'>EF0</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6lip|6lip]], [[5zj2|5zj2]], [[6lj0|6lj0]], [[6lj1|6lj1]], [[6liz|6liz]], [[6lj2|6lj2]], [[6lj4|6lj4]]</div></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaNDM-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lj5 OCA], [http://pdbe.org/6lj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lj5 RCSB], [http://www.ebi.ac.uk/pdbsum/6lj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lj5 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN]] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
beta-lactam antibiotics have long been the mainstay for the treatment of bacterial infections. New Delhi metallo-beta-lactamase 1 (NDM-1) is able to hydrolyze nearly all beta-lactam antibiotics and even clinically used serine-beta-lactamase inhibitors. The wide and rapid spreading of NDM-1 gene among pathogenic bacteria has attracted extensive attention, therefore high potency NDM-1 inhibitors are urgently needed. Here we report a series of structure-guided design of D-captopril derivatives that can inhibit the activity of NDM-1 in vitro and at cellular levels. Structural comparison indicates the mechanisms of inhibition enhancement and provides insights for further inhibitor optimization. | |||
Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.,Ma G, Wang S, Wu K, Zhang W, Ahmad A, Hao Q, Lei X, Zhang H Bioorg Med Chem. 2020 Dec 3;29:115902. doi: 10.1016/j.bmc.2020.115902. PMID:33302045<ref>PMID:33302045</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6lj5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Beta-lactamase]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ma G]] | [[Category: Ma, G]] | ||
[[Category: Zhang H]] | [[Category: Zhang, H]] | ||
[[Category: Antibiotic]] | |||
[[Category: Antibiotic resistent]] | |||
[[Category: Hydrolase]] | |||
[[Category: Inhibitor]] | |||
[[Category: Metallo-beta-lactamase]] | |||
[[Category: Ndm-1]] | |||
[[Category: Thio compound]] | |||
Revision as of 13:49, 24 December 2020
Crystal structure of NDM-1 in complex with D-captopril derivative wss04145Crystal structure of NDM-1 in complex with D-captopril derivative wss04145
Structural highlights
Function[BLAN1_KLEPN] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. Publication Abstract from PubMedbeta-lactam antibiotics have long been the mainstay for the treatment of bacterial infections. New Delhi metallo-beta-lactamase 1 (NDM-1) is able to hydrolyze nearly all beta-lactam antibiotics and even clinically used serine-beta-lactamase inhibitors. The wide and rapid spreading of NDM-1 gene among pathogenic bacteria has attracted extensive attention, therefore high potency NDM-1 inhibitors are urgently needed. Here we report a series of structure-guided design of D-captopril derivatives that can inhibit the activity of NDM-1 in vitro and at cellular levels. Structural comparison indicates the mechanisms of inhibition enhancement and provides insights for further inhibitor optimization. Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.,Ma G, Wang S, Wu K, Zhang W, Ahmad A, Hao Q, Lei X, Zhang H Bioorg Med Chem. 2020 Dec 3;29:115902. doi: 10.1016/j.bmc.2020.115902. PMID:33302045[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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