7k2x: Difference between revisions
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<StructureSection load='7k2x' size='340' side='right'caption='[[7k2x]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='7k2x' size='340' side='right'caption='[[7k2x]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7k2x]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[7k2x]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K2X 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=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7k2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k2x OCA], [https://pdbe.org/7k2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k2x RCSB], [https://www.ebi.ac.uk/pdbsum/7k2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k2x 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=7k2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k2x OCA], [https://pdbe.org/7k2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k2x RCSB], [https://www.ebi.ac.uk/pdbsum/7k2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k2x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9L5C7_ECOLX Q9L5C7_ECOLX] | |||
<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: Escherichia coli]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hu | [[Category: Hu L]] | ||
[[Category: Lu | [[Category: Lu S]] | ||
[[Category: Palzkill | [[Category: Palzkill T]] | ||
[[Category: Prasad | [[Category: Prasad BVV]] | ||
[[Category: Sankaran | [[Category: Sankaran B]] | ||
[[Category: Soeung | [[Category: Soeung V]] | ||
Latest revision as of 18:16, 18 October 2023
Crystal structure of CTX-M-14 E166A/K234R Beta-lactamaseCrystal structure of CTX-M-14 E166A/K234R Beta-lactamase
Structural highlights
FunctionPublication Abstract from PubMedLys(234) is one of the residues present in class A beta-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser(130), it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant beta-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome beta-lactamase-mediated antibiotic resistance. Here we show that for CTX-M-14 beta-lactamase, whereas Lys(234) is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in k cat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser(130), and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser(130) and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance. A drug-resistant beta-lactamase variant changes the conformation of its active-site proton shuttle to alter substrate specificity and inhibitor potency.,Soeung V, Lu S, Hu L, Judge A, Sankaran B, Prasad BVV, Palzkill T J Biol Chem. 2020 Dec 25;295(52):18239-18255. doi: 10.1074/jbc.RA120.016103. Epub, 2020 Oct 26. PMID:33109613[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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