4x55: Difference between revisions
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<StructureSection load='4x55' size='340' side='right'caption='[[4x55]], [[Resolution|resolution]] 1.94Å' scene=''> | <StructureSection load='4x55' size='340' side='right'caption='[[4x55]], [[Resolution|resolution]] 1.94Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4x55]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4x55]] is a 2 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=4X55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X55 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CTJ:1-({(2R)-2-[(1R)-1-{[(2Z)-2-(2-AMINO-1,3-THIAZOL-4-YL)-2-{[(2-CARBOXYPROPAN-2-YL)OXY]IMINO}ACETYL]AMINO}-2-OXOETHYL]-4-CARBOXY-3,6-DIHYDRO-2H-1,3-THIAZIN-5-YL}METHYL)PYRIDINIUM'>CTJ</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTJ:1-({(2R)-2-[(1R)-1-{[(2Z)-2-(2-AMINO-1,3-THIAZOL-4-YL)-2-{[(2-CARBOXYPROPAN-2-YL)OXY]IMINO}ACETYL]AMINO}-2-OXOETHYL]-4-CARBOXY-3,6-DIHYDRO-2H-1,3-THIAZIN-5-YL}METHYL)PYRIDINIUM'>CTJ</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=4x55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x55 OCA], [https://pdbe.org/4x55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x55 RCSB], [https://www.ebi.ac.uk/pdbsum/4x55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x55 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/G5DE28_ACIBA G5DE28_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: Clasman | [[Category: Clasman JR]] | ||
[[Category: June | [[Category: June CM]] | ||
[[Category: Leonard | [[Category: Leonard DA]] | ||
[[Category: Powers | [[Category: Powers RA]] | ||
Revision as of 00:13, 13 April 2023
Structure of the class D Beta-Lactamase OXA-225 K82D in Acyl-Enzyme Complex with CeftazidimeStructure of the class D Beta-Lactamase OXA-225 K82D in Acyl-Enzyme Complex with Ceftazidime
Structural highlights
FunctionPublication Abstract from PubMedThe carbapenem-hydrolyzing class D beta-lactamases OXA-23 and OXA-24/40 have emerged worldwide as causative agents for beta-lactam antibiotic resistance in Acinetobacter species. Many variants of these enzymes have appeared clinically, including OXA-160 and OXA-225, which both contain a P --> S substitution at homologous positions in the OXA-24/40 and OXA-23 backgrounds, respectively. We purified OXA-160 and OXA-225 and used steady-state kinetic analysis to compare the substrate profiles of these variants to their parental enzymes, OXA-24/40 and OXA-23. OXA-160 and OXA-225 possess greatly enhanced hydrolytic activities against aztreonam, ceftazidime, cefotaxime, and ceftriaxone when compared to OXA-24/40 and OXA-23. These enhanced activities are the result of much lower Km values, suggesting that the P --> S substitution enhances the binding affinity of these drugs. We have determined the structures of the acylated forms of OXA-160 (with ceftazidime and aztreonam) and OXA-225 (ceftazidime). These structures show that the R1 oxyimino side-chain of these drugs occupies a space near the beta5-beta6 loop and the omega loop of the enzymes. The P --> S substitution found in OXA-160 and OXA-225 results in a deviation of the beta5-beta6 loop, relieving the steric clash with the R1 side-chain carboxypropyl group of aztreonam and ceftazidime. These results reveal worrying trends in the enhancement of substrate spectrum of class D beta-lactamases but may also provide a map for beta-lactam improvement. Structural Basis of Activity against Aztreonam and Extended Spectrum Cephalosporins for Two Carbapenem-Hydrolyzing Class D beta-Lactamases from Acinetobacter baumannii.,Mitchell JM, Clasman JR, June CM, Kaitany KC, LaFleur JR, Taracila MA, Klinger NV, Bonomo RA, Wymore T, Szarecka A, Powers RA, Leonard DA Biochemistry. 2015 Mar 2. PMID:25710192[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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