Characterisation of neprilysin (EC 3.4.24.11) S-2' subsite

被引：14

作者：

Dion, N

Cohen, P

Crine, P

Boileau, G

机构：

[1] UNIV MONTREAL,FAC MED,DEPT BIOCHIM,MONTREAL,PQ H3C 3J7,CANADA

[2] CNRS URA 1682,LAB SIGNAUX REGULATEURS CELLULAIRES & MOL,PARIS,FRANCE

[3] UNIV PARIS 06,PARIS,FRANCE

来源：

FEBS LETTERS | 1997年 / 411卷 / 01期

基金：

英国医学研究理事会;

关键词：

neutral endopeptidase 24.11; enzyme-substrate interaction; mutagenesis;

D O I：

10.1016/S0014-5793(97)00681-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neprilysin is a neutral peptidase that cleaves small peptide substrates on the amino-side of hydrophobic amino acid residues. In the present study, we have used inhibition of nonmutated and mutated enzymes with dipeptide inhibitors and hydrolysis of the substrate [Leu(5), Arg(6)]enkephalin in order to evaluate the contribution of the S-2' subsite to substrate and inhibitor binding. Our results suggest that (1) Arg-102 and Asn-542 provide major contributions to the interaction of the enzyme with the P-2' residue of the substrate, (2) the S-2' subsite is vast and can accommodate bulky side chains, and (3) Arg-102 restricts access to the S-2' subsite to some side chains such as arginine. (C) 1997 Federation of European Biochemical Societies.

引用

页码：140 / 144

页数：5

共 27 条

[1] MEMBRANE-BOUND KIDNEY NEUTRAL METALLOENDOPEPTIDASE - INTERACTION WITH SYNTHETIC SUBSTRATES, NATURAL PEPTIDES, AND INHIBITORS [J].