Kelly J A, Knox J R, Zhao H, Frère J M, Ghaysen J M
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269.
J Mol Biol. 1989 Sep 20;209(2):281-95. doi: 10.1016/0022-2836(89)90277-5.
X-ray crystallography has been used to examine the binding of three members of the beta-lactam family of antibiotics to the D-alanyl-D-alanine peptidase from Streptomyces R61, a target of penicillins. Cephalosporin C, the monobactam analog of penicillin G and (2,3)-alpha-methylene benzylpenicillin have been mapped at 2.3 A resolution in the form of acyl-enzyme complexes bound to serine 62. On the basis of the positions of these inhibitors, the binding of a tripeptide substrate for the enzyme, L-lysyl-D-alanyl-D-alanine, has been modeled in the active site. The binding of both inhibitors and substrate is facilitated by hydrogen-bonding interactions with a conserved beta-strand (297-303), which is antiparallel to the beta-lactam's acylamide linkage or the substrate's peptide bond. The active site is similar to that in beta-lactamases.
X射线晶体学已被用于研究β-内酰胺类抗生素家族的三个成员与来自链霉菌R61的D-丙氨酰-D-丙氨酸肽酶的结合情况，该肽酶是青霉素的一个作用靶点。头孢菌素C、青霉素G的单环β-内酰胺类似物以及(2,3)-α-亚甲基苄青霉素已以与丝氨酸62结合的酰基酶复合物形式在2.3埃分辨率下进行了图谱分析。基于这些抑制剂的位置，已对该酶的三肽底物L-赖氨酰-D-丙氨酰-D-丙氨酸在活性位点的结合进行了建模。抑制剂和底物的结合都通过与一条保守的β链（297-303）的氢键相互作用而得到促进，该β链与β-内酰胺的酰酰胺键或底物的肽键呈反平行。其活性位点与β-内酰胺酶中的活性位点相似。
