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Chem Biol. 2001 Dec;8(12):1253-64.

Structure of cephalosporin acylase in complex with glutaryl-7-aminocephalosporanic acid and glutarate: insight into the basis of its substrate specificity.

Author information

1
School of Chemical Engineering, Yeungnam University, South Korea. ykim1@yu.ac.kr

Abstract

BACKGROUND:

Semisynthetic cephalosporins are primarily synthesized from 7-aminocephalosporanic acid (7-ACA), which is obtained by environmentally toxic chemical deacylation of cephalosporin C (CPC). Thus, the enzymatic conversion of CPC to 7-ACA by cephalosporin acylase (CA) would be of great interest. However, CAs use glutaryl-7-ACA (GL-7-ACA) as a primary substrate and the enzyme has low turnover rates for CPC.

RESULTS:

The binary complex structures of CA with GL-7-ACA and glutarate (the side-chain of GL-7-ACA) show extensive interactions between the glutaryl moiety of GL-7-ACA and the seven residues that form the side-chain pocket. These interactions explain why the D-alpha-aminoadipyl side-chain of CPC yields a poorer substrate than GL-7-ACA.

CONCLUSIONS:

This understanding of the nature of substrate specificity may be useful in the design of an enzyme with an improved performance for the conversion of CPC to 7-ACA. Additionally, the catalytic mechanism of the deacylation reaction was revealed by the ligand bound structures.

PMID:
11755403
DOI:
10.1016/s1074-5521(01)00092-8
[Indexed for MEDLINE]
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