This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6td1
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 3: | Line 3: | ||
<StructureSection load='6td1' size='340' side='right'caption='[[6td1]], [[Resolution|resolution]] 1.20Å' scene=''> | <StructureSection load='6td1' size='340' side='right'caption='[[6td1]], [[Resolution|resolution]] 1.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6td1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TD1 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6td1]] is a 1 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=6TD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TD1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=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]] 1.2Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=SO4:SULFATE+ION'>SO4</scene></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6td1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6td1 OCA], [https://pdbe.org/6td1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6td1 RCSB], [https://www.ebi.ac.uk/pdbsum/6td1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6td1 ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Klebsiella pneumoniae carbapenemase-2 (KPC-2) is a serine-beta-lactamase (SBL) capable of hydrolysing almost all beta-lactam antibiotics. We compare KPC-2 inhibition by vaborbactam, a clinically-approved monocyclic boronate, and VNRX-5133 (taniborbactam), a bicyclic boronate in late-stage clinical development. Vaborbactam inhibition is slowly reversible, whereas taniborbactam has an off-rate indicating essentially irreversible complex formation and a 15-fold higher on-rate, although both potentiate beta-lactam activity against KPC-2-expressing K. pneumoniae. High resolution X-ray crystal structures reveal closely related binding modes for both inhibitors to KPC-2, with differences apparent only in positioning of the endocyclic boronate ester oxygen. The results indicate the bicyclic boronate scaffold as both an efficient, long-lasting, KPC-2 inhibitor and capable of supporting further iterations that may improve potency against specific enzyme targets and pre-empt the emergence of inhibitor resistant KPC-2 variants. | ||
| + | |||
| + | Cyclic boronates as versatile scaffolds for KPC-2 beta-lactamase inhibition.,Tooke CL, Hinchliffe P, Krajnc A, Mulholland AJ, Brem J, Schofield CJ, Spencer J RSC Med Chem. 2020 Jan 10;11(4):491-496. doi: 10.1039/c9md00557a. eCollection , 2020 Apr 1. PMID:33479650<ref>PMID:33479650</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6td1" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Klebsiella pneumoniae]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Hinchliffe | + | [[Category: Hinchliffe P]] |
| - | [[Category: Spencer | + | [[Category: Spencer J]] |
| - | [[Category: Tooke | + | [[Category: Tooke CL]] |
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Crystal structure of VNRX-5133 (taniborbactam) bound to KPC-2
| |||||||||||
