4fcf

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{{STRUCTURE_4fcf| PDB=4fcf | SCENE= }}
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==K234R: apo structure of inhibitor resistant beta-lactamase==
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===K234R: apo structure of inhibitor resistant beta-lactamase===
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<StructureSection load='4fcf' size='340' side='right' caption='[[4fcf]], [[Resolution|resolution]] 1.09&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23252553}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4fcf]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FCF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=TAU:2-AMINOETHANESULFONIC+ACID'>TAU</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, shv1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 Klebsiella pneumoniae])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fcf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fcf RCSB], [http://www.ebi.ac.uk/pdbsum/4fcf PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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>
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[[4fcf]] is a 1 chain structure with sequence from [http://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].
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
==See Also==
==See Also==
*[[Beta-lactamase|Beta-lactamase]]
*[[Beta-lactamase|Beta-lactamase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:023252553</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Beta-lactamase]]
[[Category: Beta-lactamase]]
[[Category: Klebsiella pneumoniae]]
[[Category: Klebsiella pneumoniae]]
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[[Category: Akker, F van den.]]
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[[Category: Akker, F van den]]
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[[Category: Rodkey, E A.]]
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[[Category: Rodkey, E A]]
[[Category: Class a beta-lactamse]]
[[Category: Class a beta-lactamse]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Hydrolase-hydrolase inhibitor complex]]

Revision as of 13:00, 4 January 2015

K234R: apo structure of inhibitor resistant beta-lactamase

4fcf, resolution 1.09Å

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