Ligand-induced conformational change in penicillin acylase.

摘要: The enzyme penicillin acylase (penicillin amidohydrolase EC 3.5.1. 11) catalyses the cleavage of amide bond in benzylpenicillin G) side-chain to produce phenylacetic acid and 6-aminopenicillanic (6-APA). is great pharmaceutical importance, as product 6-APA starting point for synthesis many semi-synthetic antibiotics. Studies have shown that specific hydrolysis phenylacetamide derivatives, but more tolerant features rest substrate. It this property has led other applications enzyme, greater knowledge enzyme's structure specificity could facilitate engineering enhancing its potential chemical industrial applications. An extensive study binding a series derivatives been carried out. A measure relative degree inhibition by each compounds obtained using competitive assay, structures number these complexes determined X-ray crystallography. reveal clear rationale observed kinetic results, show also some ligands cause conformational change within pocket. This can generally be understood terms size orientation ligand active site.The results facilitated certain amino residues adopt two distinct, energetically favourable positions order accommodate variety site. provide evidence changes substrate-binding region may act switch mechanism autocatalytic processing enzyme.