1l2s

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[[Image:1l2s.jpg|left|200px]]
 
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==X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a DOCK-predicted non-covalent inhibitor==
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The line below this paragraph, containing "STRUCTURE_1l2s", creates the "Structure Box" on the page.
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<StructureSection load='1l2s' size='340' side='right'caption='[[1l2s]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94&#8491;</td></tr>
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<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>
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{{STRUCTURE_1l2s| PDB=1l2s | SCENE= }}
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<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>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l2/1l2s_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a DOCK-predicted non-covalent inhibitor'''
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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>
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==Overview==
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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.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1L2S is a [[Single protein]] structure of sequence from [http://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].
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</div>
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<div class="pdbe-citations 1l2s" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12121656 12121656]
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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[[Category: Beta-lactamase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Morandi, F.]]
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[[Category: Morandi F]]
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[[Category: Powers, R A.]]
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[[Category: Powers RA]]
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[[Category: Shoichet, B K.]]
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[[Category: Shoichet BK]]
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[[Category: Beta-lactamase/inhibitor complex]]
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[[Category: Cephalosporinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:28:36 2008''
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Current revision

X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a DOCK-predicted non-covalent inhibitor

PDB ID 1l2s

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