1l2s
From Proteopedia
(Difference between revisions)
| (14 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | [[Image:1l2s.jpg|left|200px]]<br /><applet load="1l2s" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1l2s, resolution 1.94Å" /> | ||
| - | '''X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a DOCK-predicted non-covalent inhibitor'''<br /> | ||
| - | == | + | ==X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a DOCK-predicted non-covalent inhibitor== |
| + | <StructureSection load='1l2s' size='340' side='right'caption='[[1l2s]], [[Resolution|resolution]] 1.94Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1l2s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L2S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L2S FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=STC:3-[(4-CHLOROANILINO)SULFONYL]THIOPHENE-2-CARBOXYLIC+ACID'>STC</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=1l2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l2s OCA], [https://pdbe.org/1l2s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l2s RCSB], [https://www.ebi.ac.uk/pdbsum/1l2s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l2s ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l2/1l2s_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1l2s ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
beta-lactamases are the most widespread resistance mechanisms to beta-lactam antibiotics, and there is a pressing need for novel, non-beta-lactam drugs. A database of over 200,000 compounds was docked to the active site of AmpC beta-lactamase to identify potential inhibitors. Fifty-six compounds were tested, and three had K(i) values of 650 microM or better. The best of these, 3-[(4-chloroanilino)sulfonyl]thiophene-2-carboxylic acid, was a competitive noncovalent inhibitor (K(i) = 26 microM), which also reversed resistance to beta-lactams in bacteria expressing AmpC. The structure of AmpC in complex with this compound was determined by X-ray crystallography to 1.94 A and reveals that the inhibitor interacts with key active-site residues in sites targeted in the docking calculation. Indeed, the experimentally determined conformation of the inhibitor closely resembles the prediction. The structure of the enzyme-inhibitor complex presents an opportunity to improve binding affinity in a novel series of inhibitors discovered by structure-based methods. | beta-lactamases are the most widespread resistance mechanisms to beta-lactam antibiotics, and there is a pressing need for novel, non-beta-lactam drugs. A database of over 200,000 compounds was docked to the active site of AmpC beta-lactamase to identify potential inhibitors. Fifty-six compounds were tested, and three had K(i) values of 650 microM or better. The best of these, 3-[(4-chloroanilino)sulfonyl]thiophene-2-carboxylic acid, was a competitive noncovalent inhibitor (K(i) = 26 microM), which also reversed resistance to beta-lactams in bacteria expressing AmpC. The structure of AmpC in complex with this compound was determined by X-ray crystallography to 1.94 A and reveals that the inhibitor interacts with key active-site residues in sites targeted in the docking calculation. Indeed, the experimentally determined conformation of the inhibitor closely resembles the prediction. The structure of the enzyme-inhibitor complex presents an opportunity to improve binding affinity in a novel series of inhibitors discovered by structure-based methods. | ||
| - | + | Structure-based discovery of a novel, noncovalent inhibitor of AmpC beta-lactamase.,Powers RA, Morandi F, Shoichet BK Structure. 2002 Jul;10(7):1013-23. PMID:12121656<ref>PMID:12121656</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1l2s" style="background-color:#fffaf0;"></div> | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ==See Also== | |
| + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Escherichia coli]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Morandi F]] | ||
| + | [[Category: Powers RA]] | ||
| + | [[Category: Shoichet BK]] | ||
Current revision
X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a DOCK-predicted non-covalent inhibitor
| |||||||||||
