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New page: '''Unreleased structure''' The entry 6rmf is ON HOLD Authors: Description: Category: Unreleased Structures
 
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'''Unreleased structure'''


The entry 6rmf is ON HOLD
==Crystal structure of NDM-1 with VNRX-5133==
<StructureSection load='6rmf' size='340' side='right'caption='[[6rmf]], [[Resolution|resolution]] 1.51&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rmf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RMF 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]] 1.51&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K9B:(4~{R})-4-[2-[4-(2-azanylethylamino)cyclohexyl]ethanoylamino]-3,3-bis(oxidanyl)-2-oxa-3-boranuidabicyclo[4.4.0]deca-1(10),6,8-triene-10-carboxylic+acid'>K9B</scene>, <scene name='pdbligand=K9K:(10aR)-2-(((1r,4R)-4-((2-aminoethyl)amino)cyclohexyl)methyl)-6-carboxy-4-hydroxy-4,10a-dihydro-10H-benzo[5,6][1,2]oxaborinino[2,3-b][1,4,2]oxazaborol-4-uide'>K9K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6rmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rmf OCA], [https://pdbe.org/6rmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rmf RCSB], [https://www.ebi.ac.uk/pdbsum/6rmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rmf ProSAT]</span></td></tr>
</table>
== Function ==
[https://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 ==
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.


Authors:  
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>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6rmf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Brem J]]
[[Category: Hinchliffe P]]
[[Category: Schofield CJ]]
[[Category: Spencer J]]
Retrieved from "https://proteopedia.org/6rmf"