Strynadka N C, Adachi H, Jensen S E, Johns K, Sielecki A, Betzel C, Sutoh K, James M N
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Nature. 1992 Oct 22;359(6397):700-5. doi: 10.1038/359700a0.
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.
青霉素G与大肠杆菌RTEM - 1β-内酰胺酶脱酰基缺陷突变体的分子复合物的X射线晶体结构展示了这些抗生素是如何被识别和破坏的。青霉素G作为酰基酶中间体与Ser 70的γ位共价结合。推导的催化机制在酰化过程中使用Ser 70的γ位作为进攻亲核试剂。Lys 73的ζ位氮原子作为广义碱从Ser 70夺取一个质子，并通过Ser 130的γ位将其转移到噻唑烷环氮原子上。脱酰基是由广义碱Glu 166协助的水分子对青霉素酰羰基碳进行亲核攻击来完成的。
