1l2s
From Proteopedia
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| - | [[Image:1l2s.jpg|left|200px]] | + | [[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''' | + | {{Structure |
| + | |PDB= 1l2s |SIZE=350|CAPTION= <scene name='initialview01'>1l2s</scene>, resolution 1.94Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=STC:3-[(4-CHLOROANILINO)SULFONYL]THIOPHENE-2-CARBOXYLIC ACID'>STC</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= K12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
| + | }} | ||
| + | |||
| + | '''X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a DOCK-predicted non-covalent inhibitor''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1L2S is a [ | + | 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]. |
==Reference== | ==Reference== | ||
| - | 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:// | + | 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] |
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
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[[Category: cephalosporinase]] | [[Category: cephalosporinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:25:33 2008'' |
Revision as of 10:25, 20 March 2008
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| , resolution 1.94Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | K12 (Escherichia coli) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a DOCK-predicted non-covalent inhibitor
Overview
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.
About this Structure
1L2S is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
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
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