6m5h: Difference between revisions
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==A class C beta-lactamase mutant - Y150F== | ==A class C beta-lactamase mutant - Y150F== | ||
<StructureSection load='6m5h' size='340' side='right'caption='[[6m5h]]' scene=''> | <StructureSection load='6m5h' size='340' side='right'caption='[[6m5h]], [[Resolution|resolution]] 1.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M5H OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6m5h]] 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=6M5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M5H FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</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=6m5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m5h OCA], [https://pdbe.org/6m5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m5h RCSB], [https://www.ebi.ac.uk/pdbsum/6m5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m5h ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9XB24_KLEPN Q9XB24_KLEPN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The hydrolysis of beta-lactam antibiotics by class C beta-lactamases proceeds through the acylation and the rate-determining deacylation steps mediated by the nucleophilic serine and the deacylation water, respectively. The pose of poor substrates such as carbapenems in the acylated enzyme is responsible for the low efficient deacylation reaction. Here we present the crystal structures of the Y150F variant of the ACC-1 class C beta-lactamase in the apo and acylated states. In the acylated enzyme complexed with two carbapenems, imipenem and meropenem, the lactam carbonyl oxygen is located in the oxyanion hole. However, the five-membered pyrroline ring displays a novel orientation that has not been reported so far. The ring is rotated such that its C3 carboxylate makes salt bridges with Lys67 and Ly315, which is accompanied by the side-chain rotamer change of Phe150. The C3 carboxylate is placed where the deacylation water occupies in the apo-enzyme, which, together with the displacement of the catalytic base residue at position 150, explains why carbapenems are poor substrates of ACC-1. | |||
Novel inhibition mechanism of carbapenems on the ACC-1 class C beta-lactamase.,Bae DW, Jung YE, Jeong BG, Cha SS Arch Biochem Biophys. 2020 Oct 30;693:108570. doi: 10.1016/j.abb.2020.108570., Epub 2020 Sep 1. PMID:32888908<ref>PMID:32888908</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6m5h" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Klebsiella pneumoniae]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bae DW]] | [[Category: Bae DW]] | ||
[[Category: Cha SS]] | [[Category: Cha SS]] | ||
[[Category: Jung YE]] | [[Category: Jung YE]] | ||
Latest revision as of 18:16, 29 November 2023
A class C beta-lactamase mutant - Y150FA class C beta-lactamase mutant - Y150F
Structural highlights
FunctionPublication Abstract from PubMedThe hydrolysis of beta-lactam antibiotics by class C beta-lactamases proceeds through the acylation and the rate-determining deacylation steps mediated by the nucleophilic serine and the deacylation water, respectively. The pose of poor substrates such as carbapenems in the acylated enzyme is responsible for the low efficient deacylation reaction. Here we present the crystal structures of the Y150F variant of the ACC-1 class C beta-lactamase in the apo and acylated states. In the acylated enzyme complexed with two carbapenems, imipenem and meropenem, the lactam carbonyl oxygen is located in the oxyanion hole. However, the five-membered pyrroline ring displays a novel orientation that has not been reported so far. The ring is rotated such that its C3 carboxylate makes salt bridges with Lys67 and Ly315, which is accompanied by the side-chain rotamer change of Phe150. The C3 carboxylate is placed where the deacylation water occupies in the apo-enzyme, which, together with the displacement of the catalytic base residue at position 150, explains why carbapenems are poor substrates of ACC-1. Novel inhibition mechanism of carbapenems on the ACC-1 class C beta-lactamase.,Bae DW, Jung YE, Jeong BG, Cha SS Arch Biochem Biophys. 2020 Oct 30;693:108570. doi: 10.1016/j.abb.2020.108570., Epub 2020 Sep 1. PMID:32888908[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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