1l2s
From Proteopedia
|
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 with STC as ligand. Active as Beta-lactamase, with EC number 3.5.2.6 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
Page seeded by OCA on Tue Nov 20 20:11:55 2007
