5l2f: Difference between revisions
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New page: '''Unreleased structure''' The entry 5l2f is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==High Resolution Structure of Acinetobacter baumannii beta-lactamase OXA-51 I129L/K83D bound to doripenem== | ||
<StructureSection load='5l2f' size='340' side='right'caption='[[5l2f]], [[Resolution|resolution]] 1.77Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5l2f]] 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=5L2F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L2F 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]] 1.77Å</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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5l2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l2f OCA], [https://pdbe.org/5l2f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l2f RCSB], [https://www.ebi.ac.uk/pdbsum/5l2f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l2f ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q5QT35_ACIBA Q5QT35_ACIBA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
OXA-51 is a class D beta-lactamase that is thought to be the native carbapenemase of Acinetobacter baumannii. Many variants of OXA-51 containing active site substitutions have been identified from A. baumannii isolates, and some of these substitutions increase hydrolytic activity toward carbapenem antibiotics. We have determined the high-resolution structures of apo OXA-51 and OXA-51 with one such substitution (I129L) with the carbapenem doripenem trapped in the active site as an acyl-intermediate. The structure shows that acyl-doripenem adopts an orientation very similar to carbapenem ligands observed in the active site of OXA-24/40 (doripenem) and OXA-23 (meropenem). In the OXA-51 variant/doripenem complex, the indole ring of W222 is oriented away from the doripenem binding site, thereby eliminating a clash that is predicted to occur in wildtype OXA-51. Similarly, in the OXA-51 variant complex, L129 adopts a different rotamer compared to I129 in wildtype OXA-51. This alternative position moves its side chain away from the hydroxyethyl moiety of doripenem and relieves another potential clash between the enzyme and carbapenem substrates. Molecular dynamics simulations of OXA-51 and OXA-51 I129L demonstrate that compared to isoleucine, a leucine at this position greatly favors a rotamer that accommodates the ligand. These results provide a molecular justification for how this substitution generates enhanced binding affinity for carbapenems, and therefore helps explain the prevalence of this substitution in clinical OXA-51 variants. | |||
The structure of a doripenem-bound OXA-51 class D beta-lactamase variant with enhanced carbapenemase activity.,June CM, Muckenthaler TJ, Schroder EC, Klamer ZL, Wawrzak Z, Powers RA, Szarecka A, Leonard DA Protein Sci. 2016 Sep 16. doi: 10.1002/pro.3040. PMID:27636561<ref>PMID:27636561</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5l2f" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Acinetobacter baumannii]] | |||
[[Category: Large Structures]] | |||
[[Category: June CM]] | |||
[[Category: Leonard DA]] | |||
[[Category: Muckenthaler T]] | |||
[[Category: Powers RA]] | |||
Latest revision as of 12:47, 4 October 2023
High Resolution Structure of Acinetobacter baumannii beta-lactamase OXA-51 I129L/K83D bound to doripenem
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