6sp7: Difference between revisions

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-'''Unreleased structure'''
-The entry 6sp7 is ON HOLD
+==Crystal Structure of the VIM-2 Acquired Metallo-beta-Lactamase in Complex with Taniborbactam (VNRX-5133)==
+<StructureSection load='6sp7' size='340' side='right'caption='[[6sp7]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6sp7]] 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=6SP7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SP7 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]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <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=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=6sp7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sp7 OCA], [https://pdbe.org/6sp7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sp7 RCSB], [https://www.ebi.ac.uk/pdbsum/6sp7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sp7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A major resistance mechanism in Gram-negative bacteria is the production of beta-lactamase enzymes. Originally recognized for their ability to hydrolyze penicillins, emergent beta-lactamases can now confer resistance to other beta-lactam drugs, including both cephalosporins and carbapenems. The emergence and global spread of beta-lactamase-producing multi-drug-resistant "superbugs" has caused increased alarm within the medical community due to the high mortality rate associated with these difficult-to-treat bacterial infections. To address this unmet medical need, we initiated an iterative program combining medicinal chemistry, structural biology, biochemical testing, and microbiological profiling to identify broad-spectrum inhibitors of both serine- and metallo-beta-lactamase enzymes. Lead optimization, beginning with narrower-spectrum, weakly active compounds, provided 20 (VNRX-5133, taniborbactam), a boronic-acid-containing pan-spectrum beta-lactamase inhibitor. In vitro and in vivo studies demonstrated that 20 restored the activity of beta-lactam antibiotics against carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae. Taniborbactam is the first pan-spectrum beta-lactamase inhibitor to enter clinical development.
-Authors: Docquier, J.D., Pozzi, C., De Luca, F., Benvenuti, M., Mangani, S.
+Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo-beta-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections.,Liu B, Trout REL, Chu GH, McGarry D, Jackson RW, Hamrick JC, Daigle DM, Cusick SM, Pozzi C, De Luca F, Benvenuti M, Mangani S, Docquier JD, Weiss WJ, Pevear DC, Xerri L, Burns CJ J Med Chem. 2019 Dec 16. doi: 10.1021/acs.jmedchem.9b01518. PMID:31765155<ref>PMID:31765155</ref>
-Description: Crystal Structure of the VIM-2 Acquired Metallo-beta-Lactamase in Complex with Taniborbactam (VNRX-5133)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Benvenuti, M]]
+<div class="pdbe-citations 6sp7" style="background-color:#fffaf0;"></div>
-[[Category: De Luca, F]]
-[[Category: Mangani, S]]
+==See Also==
-[[Category: Docquier, J.D]]
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
-[[Category: Pozzi, C]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Pseudomonas aeruginosa]]
+[[Category: Benvenuti M]]
+[[Category: De Luca F]]
+[[Category: Docquier JD]]
+[[Category: Mangani S]]
+[[Category: Pozzi C]]