3o86: Difference between revisions
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<StructureSection load='3o86' size='340' side='right'caption='[[3o86]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='3o86' size='340' side='right'caption='[[3o86]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3o86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3o86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O86 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]] 1.6Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BSF:{[(BENZYLSULFONYL)AMINO]METHYL}BORONIC+ACID'>BSF</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id=' | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3o86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o86 OCA], [https://pdbe.org/3o86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o86 RCSB], [https://www.ebi.ac.uk/pdbsum/3o86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o86 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=3o86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o86 OCA], [https://pdbe.org/3o86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o86 RCSB], [https://www.ebi.ac.uk/pdbsum/3o86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o86 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. | |||
<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 K-12]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Eidam | [[Category: Eidam O]] | ||
[[Category: Karpiak | [[Category: Karpiak J]] | ||
[[Category: Romagnoli | [[Category: Romagnoli C]] | ||
[[Category: Shoichet | [[Category: Shoichet BK]] | ||
Latest revision as of 12:30, 6 September 2023
Crystal structure of AmpC beta-lactamase in complex with a sulfonamide boronic acid inhibitorCrystal structure of AmpC beta-lactamase in complex with a sulfonamide boronic acid inhibitor
Structural highlights
FunctionAMPC_ECOLI This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. Publication Abstract from PubMedWe investigated a series of sulfonamide boronic acids that resulted from the merging of two unrelated AmpC beta-lactamase inhibitor series. The new boronic acids differed in the replacement of the canonical carboxamide, found in all penicillin and cephalosporin antibiotics, with a sulfonamide. Surprisingly, these sulfonamides had a highly distinct structure-activity relationship from the previously explored carboxamides, high ligand efficiencies (up to 0.91), and K(i) values down to 25 nM and up to 23 times better for smaller analogues. Conversely, K(i) values were 10-20 times worse for larger molecules than in the carboxamide congener series. X-ray crystal structures (1.6-1.8 A) of AmpC with three of the new sulfonamides suggest that this altered structure-activity relationship results from the different geometry and polarity of the sulfonamide versus the carboxamide. The most potent inhibitor reversed beta-lactamase-mediated resistance to third generation cephalosporins, lowering their minimum inhibitory concentrations up to 32-fold in cell culture. Design, Synthesis, Crystal Structures, and Antimicrobial Activity of Sulfonamide Boronic Acids as beta-Lactamase Inhibitors.,Eidam O, Romagnoli C, Caselli E, Babaoglu K, Pohlhaus DT, Karpiak J, Bonnet R, Shoichet BK, Prati F J Med Chem. 2010 Oct 14. PMID:20945905[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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