6sp6: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6sp6' size='340' side='right'caption='[[6sp6]], [[Resolution|resolution]] 1.10Å' scene=''> | <StructureSection load='6sp6' size='340' side='right'caption='[[6sp6]], [[Resolution|resolution]] 1.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6sp6]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6sp6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SP6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SP6 FirstGlance]. <br> | ||
</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=KJK:(3~{R})-3-[2-[4-(2-azanylethylamino)cyclohexyl]ethanoylamino]-2-oxidanyl-3,4-dihydro-1,2-benzoxaborinine-8-carboxylic+acid'>KJK</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1Å</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=KJK:(3~{R})-3-[2-[4-(2-azanylethylamino)cyclohexyl]ethanoylamino]-2-oxidanyl-3,4-dihydro-1,2-benzoxaborinine-8-carboxylic+acid'>KJK</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6sp6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sp6 OCA], [https://pdbe.org/6sp6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sp6 RCSB], [https://www.ebi.ac.uk/pdbsum/6sp6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sp6 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A223A5J4_ECOLX A0A223A5J4_ECOLX] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 6sp6" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6sp6" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Benvenuti | [[Category: Benvenuti M]] | ||
[[Category: | [[Category: De Luca F]] | ||
[[Category: | [[Category: Docquier JD]] | ||
[[Category: Mangani | [[Category: Mangani S]] | ||
[[Category: Pozzi | [[Category: Pozzi C]] | ||
Latest revision as of 15:45, 24 January 2024
Ultra-high Resolution Crystal Structure of the CTX-M-15 Extended-Spectrum beta-Lactamase in Complex with Taniborbactam (VNRX-5133)Ultra-high Resolution Crystal Structure of the CTX-M-15 Extended-Spectrum beta-Lactamase in Complex with Taniborbactam (VNRX-5133)
Structural highlights
FunctionPublication Abstract from PubMedA 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||