6rtn: Difference between revisions
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New page: '''Unreleased structure''' The entry 6rtn is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures |
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==Crystal structure of OXA-10 with VNRX-5133== | |||
<StructureSection load='6rtn' size='340' side='right'caption='[[6rtn]], [[Resolution|resolution]] 2.17Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6rtn]] 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=6RTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RTN 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]] 2.17Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=KJK:(3~{R})-3-[2-[4-(2-azanylethylamino)cyclohexyl]ethanoylamino]-2-oxidanyl-3,4-dihydro-1,2-benzoxaborinine-8-carboxylic+acid'>KJK</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=6rtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rtn OCA], [https://pdbe.org/6rtn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rtn RCSB], [https://www.ebi.ac.uk/pdbsum/6rtn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rtn ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLO10_PSEAI BLO10_PSEAI] Hydrolyzes both carbenicillin and oxacillin. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The bicyclic boronate VNRX-5133 (taniborbactam) is a new type of beta-lactamase inhibitor in clinical development. We report that VNRX-5133 inhibits serine-beta-lactamases (SBLs) and some clinically important metallo-beta-lactamases (MBLs), including NDM-1 and VIM-1/2. VNRX-5133 activity against IMP-1 and tested B2/B3 MBLs was lower/not observed. Crystallography reveals how VNRX-5133 binds to the class D SBL OXA-10 and MBL NDM-1. The crystallographic results highlight the ability of bicyclic boronates to inhibit SBLs and MBLs via binding of a tetrahedral (sp(3)) boron species. The structures imply conserved binding of the bicyclic core with SBLs/MBLs. With NDM-1, by crystallography, we observed an unanticipated VNRX-5133 binding mode involving cyclization of its acylamino oxygen onto the boron of the bicyclic core. Different side-chain binding modes for bicyclic boronates for SBLs and MBLs imply scope for side-chain optimization. The results further support the "high-energy-intermediate" analogue approach for broad-spectrum beta-lactamase inhibitor development and highlight the ability of boron inhibitors to interchange between different hybridization states/binding modes. | |||
Bicyclic Boronate VNRX-5133 Inhibits Metallo- and Serine-beta-Lactamases.,Krajnc A, Brem J, Hinchliffe P, Calvopina K, Panduwawala TD, Lang PA, Kamps JJAG, Tyrrell JM, Widlake E, Saward BG, Walsh TR, Spencer J, Schofield CJ J Med Chem. 2019 Sep 26;62(18):8544-8556. doi: 10.1021/acs.jmedchem.9b00911. Epub, 2019 Sep 16. PMID:31454231<ref>PMID:31454231</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6rtn" 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: Brem J]] | |||
[[Category: Schofield C]] | |||
Latest revision as of 12:28, 24 January 2024
Crystal structure of OXA-10 with VNRX-5133
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