7ayj
From Proteopedia
(Difference between revisions)
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<StructureSection load='7ayj' size='340' side='right'caption='[[7ayj]], [[Resolution|resolution]] 1.21Å' scene=''> | <StructureSection load='7ayj' size='340' side='right'caption='[[7ayj]], [[Resolution|resolution]] 1.21Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AYJ 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]] 1.21Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.21Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=S9N:3-(4-fluorophenyl)-1-sulfamoyl-pyrrole-2-carboxylic+acid'>S9N</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=S9N:3-(4-fluorophenyl)-1-sulfamoyl-pyrrole-2-carboxylic+acid'>S9N</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=7ayj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ayj OCA], [https://pdbe.org/7ayj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ayj RCSB], [https://www.ebi.ac.uk/pdbsum/7ayj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ayj ProSAT]</span></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=7ayj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ayj OCA], [https://pdbe.org/7ayj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ayj RCSB], [https://www.ebi.ac.uk/pdbsum/7ayj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ayj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Function == | ||
| - | [https://www.uniprot.org/uniprot/Q9XAY4_PSEAI Q9XAY4_PSEAI] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Metallo-beta-lactamases (MBLs) can efficiently catalyze the hydrolysis of all classes of beta-lactam antibiotics except monobactams. While serine-beta-lactamase (SBL) inhibitors (e.g., clavulanic acid, avibactam) are established for clinical use, no such MBL inhibitors are available. We report on the synthesis and mechanism of inhibition of N-sulfamoylpyrrole-2-carboxylates (NSPCs) which are potent inhibitors of clinically relevant B1 subclass MBLs, including NDM-1. Crystallography reveals that the N-sulfamoyl NH2 group displaces the dizinc bridging hydroxide/water of the B1 MBLs. Comparison of crystal structures of an NSPC and taniborbactam (VRNX-5133), presently in Phase III clinical trials, shows similar binding modes for the NSPC and the cyclic boronate ring systems. The presence of an NSPC restores meropenem efficacy in clinically derived E. coli and K. pneumoniae blaNDM-1. The results support the potential of NSPCs and related compounds as efficient MBL inhibitors, though further optimization is required for their clinical development. | ||
| - | |||
| - | Structural Basis of Metallo-beta-lactamase Inhibition by N-Sulfamoylpyrrole-2-carboxylates.,Farley AJM, Ermolovich Y, Calvopina K, Rabe P, Panduwawala T, Brem J, Bjorkling F, Schofield CJ ACS Infect Dis. 2021 May 18. doi: 10.1021/acsinfecdis.1c00104. PMID:34003651<ref>PMID:34003651</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 7ayj" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Pseudomonas aeruginosa]] | ||
[[Category: Brem J]] | [[Category: Brem J]] | ||
[[Category: Calvopina K]] | [[Category: Calvopina K]] | ||
Current revision
Metallo beta-lactamse Vim-1 with a sulfamoyl inhibitor.
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