4y0u: Difference between revisions
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<StructureSection load='4y0u' size='340' side='right'caption='[[4y0u]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='4y0u' size='340' side='right'caption='[[4y0u]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4y0u]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4y0u]] 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=4Y0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y0U FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALP:2-(1-CARBOXY-2-HYDROXY-ETHYL)-5,5-DIMETHYL-THIAZOLIDINE-4-CARBOXYLIC+ACID'>ALP</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALP:2-(1-CARBOXY-2-HYDROXY-ETHYL)-5,5-DIMETHYL-THIAZOLIDINE-4-CARBOXYLIC+ACID'>ALP</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=4y0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0u OCA], [https://pdbe.org/4y0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y0u RCSB], [https://www.ebi.ac.uk/pdbsum/4y0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0u ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q2TR58_ACIBA Q2TR58_ACIBA] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Acinetobacter baumannii]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gill | [[Category: Gill P]] | ||
[[Category: Golemi-Kotra | [[Category: Golemi-Kotra D]] | ||
[[Category: Katiki | [[Category: Katiki M]] | ||
[[Category: Kumar | [[Category: Kumar P]] | ||
[[Category: Pratap | [[Category: Pratap S]] | ||
Latest revision as of 21:01, 26 April 2023
Crystal Structure of 6Alpha-Hydroxymethylpenicillanate Complexed with OXA-58, a Carbapenem hydrolyzing Class D betalactamase from Acinetobacter baumanii.Crystal Structure of 6Alpha-Hydroxymethylpenicillanate Complexed with OXA-58, a Carbapenem hydrolyzing Class D betalactamase from Acinetobacter baumanii.
Structural highlights
FunctionPublication Abstract from PubMedCarbapenem-hydrolyzing class D beta-lactamases (CHDLs) are a subgroup of class D beta-lactamases, which are enzymes that hydrolyze beta-lactams. They have attracted interest due to the emergence of multidrug-resistant Acinetobacter baumannii, which is not responsive to treatment with carbapenems, the usual antibiotics of choice for this bacterium. Unlike other class D beta-lactamases, these enzymes efficiently hydrolyze carbapenem antibiotics. To explore the structural requirements for the catalysis of carbapenems by these enzymes, we determined the crystal structure of the OXA-58 CHDL of A. baumannii following acylation of its active-site serine by a 6alpha-hydroxymethyl penicillin derivative that is a structural mimetic for a carbapenem. In addition, several point mutation variants of the active site of OXA-58, as identified by the crystal structure analysis, were characterized kinetically. These combined studies confirm the mechanistic relevance of a hydrophobic bridge formed over the active site. This structural feature is suggested to stabilize the hydrolysis-productive acyl-enzyme species formed from the carbapenem substrates of this enzyme. Furthermore, our structural studies provide strong evidence that the hydroxyethyl group of carbapenems samples different orientations in the active sites of CHDLs, and the optimum orientation for catalysis depends on the topology of the active site allowing proper closure of the active site. We propose that CHDLs use the plasticity of the active site to drive the mechanism of carbapenem hydrolysis toward efficiency. Active-Site Plasticity Is Essential to Carbapenem Hydrolysis by OXA-58 Class D beta-Lactamase of Acinetobacter baumannii.,Pratap S, Katiki M, Gill P, Kumar P, Golemi-Kotra D Antimicrob Agents Chemother. 2015 Oct 12;60(1):75-86. doi: 10.1128/AAC.01393-15. PMID:26459904[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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