4xuz
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==Structure of CTX-M-15 bound to RPX-7009 at 1.5 A== |
| + | <StructureSection load='4xuz' size='340' side='right' caption='[[4xuz]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4xuz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XUZ 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=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xux|4xux]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xuz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xuz RCSB], [http://www.ebi.ac.uk/pdbsum/4xuz PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The 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<ref>PMID:25782055</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| - | [[Category: Clifton, M | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Beta-lactamase]] | ||
| + | [[Category: Clifton, M C]] | ||
[[Category: Gardberg, A]] | [[Category: Gardberg, A]] | ||
| + | [[Category: Hydrolase-antibiotic complex]] | ||
Revision as of 13:16, 1 April 2015
Structure of CTX-M-15 bound to RPX-7009 at 1.5 A
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