3opl: Difference between revisions
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==ESBL R164H mutant SHV-1 beta-lactamase== | ==ESBL R164H mutant SHV-1 beta-lactamase== | ||
<StructureSection load='3opl' size='340' side='right' caption='[[3opl]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='3opl' size='340' side='right'caption='[[3opl]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3opl]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3opl]] is a 1 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=3OPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OPL 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]] 1.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3opl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3opl OCA], [https://pdbe.org/3opl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3opl RCSB], [https://www.ebi.ac.uk/pdbsum/3opl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3opl 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/BLA1_KLEPN BLA1_KLEPN] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==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: Sampson | [[Category: Sampson JM]] | ||
[[Category: | [[Category: Van den Akker F]] | ||
Latest revision as of 12:43, 6 September 2023
ESBL R164H mutant SHV-1 beta-lactamaseESBL R164H mutant SHV-1 beta-lactamase
Structural highlights
FunctionPublication Abstract from PubMedAmong Gram-negative bacteria, resistance to beta-lactams is mediated primarily by beta-lactamases (EC 3.2.6.5), periplasmic enzymes that inactivate beta-lactam antibiotics. Substitutions at critical amino acid positions in the class A beta-lactamase families result in enzymes that can hydrolyze extended-spectrum cephalosporins, thus demonstrating an "extended-spectrum" beta-lactamase (ESBL) phenotype. Using SHV ESBLs with substitutions in the Omega loop (R164H and R164S) as target enzymes to understand this enhanced biochemical capability and to serve as a basis for novel beta-lactamase inhibitor development, we determined the spectra of activity and crystal structures of these variants. We also studied the inactivation of the R164H and R164S mutants with tazobactam and SA2-13, a unique beta-lactamase inhibitor that undergoes a distinctive reaction chemistry in the active site. We noted that the reduced Ki values for the R164H and R164S mutants with SA2-13 are comparable to those with tazobactam (submicromolar). The apo enzyme crystal structures of the R164H and R164S SHV variants revealed an ordered Omega loop architecture that became disordered when SA2-13 was bound. Important structural alterations that result from the binding of SA2-13 explain the enhanced susceptibility of these ESBL enzymes to this inhibitor and highlight ligand-dependent Omega loop flexibility as a mechanism for accommodating and hydrolyzing beta-lactam substrates. Ligand-dependent disorder of the Omega loop observed in extended-spectrum SHV-type beta-lactamase.,Sampson JM, Ke W, Bethel CR, Pagadala SR, Nottingham MD, Bonomo RA, Buynak JD, van den Akker F Antimicrob Agents Chemother. 2011 May;55(5):2303-9. Epub 2011 Feb 28. PMID:21357298[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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