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| | ==K234R: apo structure of inhibitor resistant beta-lactamase== | | ==K234R: apo structure of inhibitor resistant beta-lactamase== |
| - | <StructureSection load='4fcf' size='340' side='right' caption='[[4fcf]], [[Resolution|resolution]] 1.09Å' scene=''> | + | <StructureSection load='4fcf' size='340' side='right'caption='[[4fcf]], [[Resolution|resolution]] 1.09Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fcf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. 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> | + | <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='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> | + | </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='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 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</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='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>
| + | <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> |
| - | <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://pdbe.org/4fcf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fcf RCSB], [http://www.ebi.ac.uk/pdbsum/4fcf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fcf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| - | *[[Beta-lactamase|Beta-lactamase]] | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Klebsiella pneumoniae]] |
| - | [[Category: Akker, F van den]] | + | [[Category: Large Structures]] |
| - | [[Category: Rodkey, E A]] | + | [[Category: Rodkey EA]] |
| - | [[Category: Class a beta-lactamse]] | + | [[Category: Van den Akker F]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Design and exploration of novel boronic acid inhibitors reveals important interactions with a clavulanic acid-resistant sulfhydryl-variable (SHV) beta-lactamase. J Med Chem. 2013 Feb 14;56(3):1084-97. doi: 10.1021/jm301490d. Epub 2013 Feb 4. PMID:23252553 doi:10.1021/jm301490d
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