4xux: Difference between revisions
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<StructureSection load='4xux' size='340' side='right'caption='[[4xux]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='4xux' size='340' side='right'caption='[[4xux]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4xux]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4xux]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XUX FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4D6:{(3R,6S)-2-HYDROXY-3-[(THIOPHEN-2-YLACETYL)AMINO]-1,2-OXABORINAN-6-YL}ACETIC+ACID'>4D6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4D6:{(3R,6S)-2-HYDROXY-3-[(THIOPHEN-2-YLACETYL)AMINO]-1,2-OXABORINAN-6-YL}ACETIC+ACID'>4D6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</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=4xux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xux OCA], [https://pdbe.org/4xux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xux RCSB], [https://www.ebi.ac.uk/pdbsum/4xux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xux ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/AMPC_ENTCL AMPC_ENTCL] 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: Enterobacter cloacae]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Abendroth | [[Category: Abendroth J]] | ||
[[Category: Clifton | [[Category: Clifton MC]] | ||
Latest revision as of 10:49, 27 September 2023
Structure of ampC bound to RPX-7009 at 1.75 AStructure of ampC bound to RPX-7009 at 1.75 A
Structural highlights
FunctionAMPC_ENTCL This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. Publication Abstract from PubMedThe increasing dissemination of carbapenemases in Gram-negative bacteria has threatened the clinical usefulness of the beta-lactam class of antimicrobials. A program was initiated to discover a new series of serine beta-lactamase inhibitors containing a boronic acid pharmacophore, with the goal of finding a potent inhibitor of serine carbapenemase enzymes that are currently compromising the utility of the carbapenem class of antibacterials. Potential lead structures were screened in silico by modeling into the active sites of key serine beta-lactamases. Promising candidate molecules were synthesized and evaluated in biochemical and whole-cell assays. Inhibitors were identified with potent inhibition of serine carbapenemases, particularly the Klebsiella pneumoniae carbapenemase (KPC), with no inhibition of mammalian serine proteases. Studies in vitro and in vivo show that RPX7009 (9f) is a broad-spectrum inhibitor, notably restoring the activity of carbapenems against KPC-producing strains. Combined with a carbapenem, 9f is a promising product for the treatment of multidrug resistant Gram-negative bacteria. Discovery of a Cyclic Boronic Acid beta-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases.,Hecker SJ, Reddy KR, Totrov M, Hirst GC, Lomovskaya O, Griffith DC, King P, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Clifton MC, Atkins K, Raymond A, Potts KT, Abendroth J, Boyer SH, Loutit JS, Morgan EE, Durso S, Dudley MN J Med Chem. 2015 Mar 17. PMID:25782055[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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