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.
4s2k
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| + | |||
==OXA-48 in complex with Avibactam at pH 7.5== | ==OXA-48 in complex with Avibactam at pH 7.5== | ||
<StructureSection load='4s2k' size='340' side='right' caption='[[4s2k]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='4s2k' size='340' side='right' caption='[[4s2k]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| Line 5: | Line 6: | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr> | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4s2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4s2k RCSB], [http://www.ebi.ac.uk/pdbsum/4s2k PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4s2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s2k OCA], [http://pdbe.org/4s2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s2k RCSB], [http://www.ebi.ac.uk/pdbsum/4s2k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s2k ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Emerging beta-lactamase-mediated resistance is threatening the clinical utility of the single most prominent class of antibacterial agents used in medicine, the beta-lactams. The diazabicyclooctane avibactam is able to inhibit a wider range of serine beta-lactamases than has been previously observed with beta-lactamase inhibitors such as the widely prescribed clavulanic acid. However, despite its broad-spectrum activity, variable levels of inhibition have been observed for molecular class D beta-lactamases. In order to better understand the molecular basis and spectrum of inhibition by avibactam, we provide structural and mechanistic analysis of the compound in complex with important class A and D serine beta-lactamases. Herein, we reveal the 1.7- and 2.0-A-resolution crystal structures of avibactam covalently bound to class D beta-lactamases OXA-10 and OXA-48. Furthermore, a kinetic analysis of key active-site mutants for class A beta-lactamase CTX-M-15 allows us to propose a validated mechanism for avibactam-mediated beta-lactamase inhibition including a unique role for S130, which acts as a general base. This study provides molecular insights that will aid in the design and development of avibactam-based chemotherapeutic agents effective against emerging drug-resistant microorganisms. | ||
| + | |||
| + | Molecular Mechanism of Avibactam-Mediated beta-Lactamase Inhibition.,King DT, King AM, Lal SM, Wright GD, Strynadka NC ACS Infect Dis. 2015 Apr 10;1(4):175-84. doi: 10.1021/acsinfecdis.5b00007. Epub, 2015 Feb 11. PMID:27622530<ref>PMID:27622530</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4s2k" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase|Beta-lactamase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 09:32, 3 October 2016
OXA-48 in complex with Avibactam at pH 7.5
| |||||||||||
