1ll9
Crystal Structure Of AmpC beta-Lactamase From E. Coli In Complex With AmoxicillinCrystal Structure Of AmpC beta-Lactamase From E. Coli In Complex With Amoxicillin
Structural highlights
FunctionAMPC_ECOLI This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedbeta-lactamases confer resistance to beta-lactam antibiotics such as penicillins and cephalosporins. However, beta-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of beta-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R(1) side chain of beta-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective beta-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design. Using steric hindrance to design new inhibitors of class C beta-lactamases.,Trehan I, Morandi F, Blaszczak LC, Shoichet BK Chem Biol. 2002 Sep;9(9):971-80. PMID:12323371[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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