5f1f: Difference between revisions
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<StructureSection load='5f1f' size='340' side='right'caption='[[5f1f]], [[Resolution|resolution]] 1.55Å' scene=''> | <StructureSection load='5f1f' size='340' side='right'caption='[[5f1f]], [[Resolution|resolution]] 1.55Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5f1f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[5f1f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_aerogenes Klebsiella aerogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F1F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F1F 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]] 1.548Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</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=5f1f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f1f OCA], [https://pdbe.org/5f1f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f1f RCSB], [https://www.ebi.ac.uk/pdbsum/5f1f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f1f ProSAT]</span></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=5f1f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f1f OCA], [https://pdbe.org/5f1f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f1f RCSB], [https://www.ebi.ac.uk/pdbsum/5f1f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f1f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q99QC1_KLEAE Q99QC1_KLEAE] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.[ARBA:ARBA00003808] | |||
<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: Klebsiella aerogenes]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: An | [[Category: An YJ]] | ||
[[Category: Cha | [[Category: Cha SS]] | ||
[[Category: Kim | [[Category: Kim MK]] | ||
[[Category: Na | [[Category: Na JH]] | ||
Revision as of 11:40, 12 July 2023
Crystal structure of CMY-10 adenylylated by acetyl-AMPCrystal structure of CMY-10 adenylylated by acetyl-AMP
Structural highlights
FunctionQ99QC1_KLEAE This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.[ARBA:ARBA00003808] Publication Abstract from PubMedObjectives: : Investigation into the adenylylation of the nucleophilic serine in AmpC BER and CMY-10 extended-spectrum class C beta-lactamases. Methods: : The formation and the stability of the adenylate adduct were examined by X-ray crystallography and MS. Inhibition assays for kinetic parameters were performed by monitoring the hydrolytic activity of AmpC BER and CMY-10 using nitrocefin as a reporter substrate. The effect of adenosine 5'-(P-acetyl)monophosphate (acAMP) on the MIC of ceftazidime was tested with four Gram-negative clinical isolates. Results: : The crystal structures and MS analyses confirmed the acAMP-mediated adenylylation of the nucleophilic serine in AmpC BER and CMY-10. acAMP inhibited AmpC BER and CMY-10 through the adenylylation of the nucleophilic serine, which could be modelled as a two-step mechanism. The initial non-covalent binding of acAMP to the active site is followed by the covalent attachment of its AMP moiety to the nucleophilic serine. The inhibition efficiencies ( k inact / K I ) of acAMP against AmpC BER and CMY-10 were determined to be 320 and 140 M -1 s -1 , respectively. The combination of ceftazidime and acAMP reduced the MIC of ceftazidime against the tested bacteria. Conclusions: : Our structural and kinetic studies revealed the detailed mechanism of adenylylation of the nucleophilic serine and may serve as a starting point for the design of novel class C beta-lactamase inhibitors on the basis of the nucleotide scaffold. Structural and mechanistic insights into the inhibition of class C beta-lactamases through the adenylylation of the nucleophilic serine.,Kim MK, An YJ, Na JH, Seol JH, Ryu JY, Lee JW, Kang LW, Chung KM, Lee JH, Moon JH, Lee JS, Cha SS J Antimicrob Chemother. 2017 Mar 1;72(3):735-743. doi: 10.1093/jac/dkw491. PMID:27999057[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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