8sq8: Difference between revisions

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-'''Unreleased structure'''
-The entry 8sq8 is ON HOLD
+==X-ray crystal structure of Acinetobacter baumanii beta-lactamase variant OXA-109 in complex with doripenem==
+<StructureSection load='8sq8' size='340' side='right'caption='[[8sq8]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8sq8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SQ8 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]] 2.27&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4J6:(4R,5S)-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-3-({(3S,5S)-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL}SULFANYL)-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>4J6</scene>, <scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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=8sq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sq8 OCA], [https://pdbe.org/8sq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sq8 RCSB], [https://www.ebi.ac.uk/pdbsum/8sq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sq8 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A8JZR7_ACIBA A8JZR7_ACIBA]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+OXA-66 is a member of the OXA-51 subfamily of class D beta-lactamases native to the Acinetobacter genus that includes Acinetobacter baumannii, one of the ESKAPE pathogens and a major cause of drug-resistant nosocomial infections. Although both wild type OXA-66 and OXA-51 have low catalytic activity, they are ubiquitous in the Acinetobacter genomes. OXA-51 is also remarkably thermostable. In addition, newly emerging, single and double amino acid variants show increased activity against carbapenems, indicating that the OXA-51 subfamily is growing and gaining clinical significance. In this study, we used molecular dynamics simulations, X-ray crystallography, and thermal denaturation data to examine and compare the dynamics of OXA-66 wt and its gain-of-function variants: I129L (OXA-83), L167V (OXA-82), P130Q (OXA-109), P130A, and W222L (OXA-234). Our data indicate that OXA-66 wt also has a high melting temperature, and its remarkable stability is due to an extensive and rigid hydrophobic bridge formed by a number of residues around the active site and harbored by the three loops, P, Omega, and beta5-beta6. Compared to the WT enzyme, the mutants exhibit higher flexibility only in the loop regions, and are more stable than other robust carbapenemases, such as OXA-23 and OXA-24/40. All the mutants show increased rotational flexibility of residues I129 and W222, which allows carbapenems to bind. Overall, our data support the hypothesis that structural features in OXA-51 and OXA-66 promote evolution of multiple highly stable variants with increased clinical relevance in A. baumannii.
-Authors:
+Structural and Dynamic Features of Acinetobacter baumannii OXA-66 beta-Lactamase Explain Its Stability and Evolution of Novel Variants.,Klamer ZL, June CM, Wawrzak Z, Taracila MA, Grey JA, Benn AMI, Russell CP, Bonomo RA, Powers RA, Leonard DA, Szarecka A J Mol Biol. 2024 May 8;436(12):168603. doi: 10.1016/j.jmb.2024.168603. PMID:38729259<ref>PMID:38729259</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8sq8" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Acinetobacter baumannii]]
+[[Category: Large Structures]]
+[[Category: June CM]]
+[[Category: Leonard DA]]
+[[Category: Powers RA]]
+[[Category: Szarecka A]]
+[[Category: Wawrzak Z]]