4fcf: Difference between revisions
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New page: '''Unreleased structure''' The entry 4fcf is ON HOLD Authors: Rodkey, E.A., van den Akker, F. Description: Crystal structure of a pre-acylation complex of sulbactam bound to a sulfenam... |
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The | ==K234R: apo structure of inhibitor resistant beta-lactamase== | ||
<StructureSection load='4fcf' size='340' side='right'caption='[[4fcf]], [[Resolution|resolution]] 1.09Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4fcf]] 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=4FCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FCF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.09Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=TAU:2-AMINOETHANESULFONIC+ACID'>TAU</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=4fcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fcf OCA], [https://pdbe.org/4fcf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fcf RCSB], [https://www.ebi.ac.uk/pdbsum/4fcf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fcf ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inhibitor resistant (IR) class A beta-lactamases pose a significant threat to many current antibiotic combinations. The K234R substitution in the SHV beta-lactamase, from Klebsiella pneumoniae , results in resistance to ampicillin/clavulanate. After site-saturation mutagenesis of Lys-234 in SHV, microbiological and biochemical characterization of the resulting beta-lactamases revealed that only -Arg conferred resistance to ampicillin/clavulanate. X-ray crystallography revealed two conformations of Arg-234 and Ser-130 in SHV K234R. The movement of Ser-130 is the principal cause of the observed clavulanate resistance. A panel of boronic acid inhibitors was designed and tested against SHV-1 and SHV K234R. A chiral ampicillin analogue was discovered to have a 2.4 +/- 0.2 nM K(i) for SHV K234R; the chiral ampicillin analogue formed a more complex hydrogen-bonding network in SHV K234R vs SHV-1. Consideration of the spatial position of Ser-130 and Lys-234 and this hydrogen-bonding network will be important in the design of novel antibiotics targeting IR beta-lactamases. | |||
Design and exploration of novel boronic acid inhibitors reveals important interactions with a clavulanic acid-resistant sulfhydryl-variable (SHV) beta-lactamase.,Winkler ML, Rodkey EA, Taracila MA, Drawz SM, Bethel CR, Papp-Wallace KM, Smith KM, Xu Y, Dwulit-Smith JR, Romagnoli C, Caselli E, Prati F, van den Akker F, Bonomo RA J Med Chem. 2013 Feb 14;56(3):1084-97. doi: 10.1021/jm301490d. Epub 2013 Feb 4. PMID:23252553<ref>PMID:23252553</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4fcf" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae]] | |||
[[Category: Large Structures]] | |||
[[Category: Rodkey EA]] | |||
[[Category: Van den Akker F]] | |||
Latest revision as of 02:52, 21 November 2024
K234R: apo structure of inhibitor resistant beta-lactamase
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