Molecular structure of the acyl-enzyme intermediate in beta-lactam hydrolysis at 1.7 A resolution. |
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Authors: | N C Strynadka H Adachi S E Jensen K Johns A Sielecki C Betzel K Sutoh M N James |
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Institution: | Department of Biochemistry, University of Alberta, Edmonton, Canada. |
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Abstract: | The X-ray crystal structure of the molecular complex of penicillin G with a deacylation-defective mutant of the RTEM-1 beta-lactamase from Escherichia coli shows how these antibiotics are recognized and destroyed. Penicillin G is covalently bound to Ser 70 0 gamma as an acyl-enzyme intermediate. The deduced catalytic mechanism uses Ser 70 0 gamma as the attacking nucleophile during acylation. Lys 73 N zeta acts as a general base in abstracting a proton from Ser 70 and transferring it to the thiazolidine ring nitrogen atom via Ser 130 0 gamma. Deacylation is accomplished by nucleophilic attack on the penicilloyl carbonyl carbon by a water molecule assisted by the general base, Glu 166. |
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