4s2k: Difference between revisions
No edit summary |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| 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=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4s2k]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S2K OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4s2k]] is a 4 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=4S2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S2K FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</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=4s2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s2k OCA], [https://pdbe.org/4s2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s2k RCSB], [https://www.ebi.ac.uk/pdbsum/4s2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s2k ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 19: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Klebsiella pneumoniae]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: King DT]] | ||
[[Category: | [[Category: Strynadka NCJ]] | ||
Latest revision as of 21:01, 20 September 2023
OXA-48 in complex with Avibactam at pH 7.5OXA-48 in complex with Avibactam at pH 7.5
Structural highlights
FunctionPublication Abstract from PubMedEmerging 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||