Characterisation of neprilysin (EC 3.4.24.11) S2′ subsite

FEBS Letters

Cohen, Paul²  Boileau, Guy¹  Dion, Natalie¹  Crine, Philippe¹ 

[1] Département de Biochimie, Faculté de Médecine, Université de Montréal, C.P. Succ. Centre-Ville Montréal, Québec H3C 3J7, Canada;Laboratoire des signaux régulateurs cellulaires et moléculaires, CNRS URA 1682, and Université Pierre et Marie Curie, Paris, France

关键词: Neutral endopeptidase 24.11;    Enzyme-substrate interaction;    Mutagenesis;    CALLA;    common acute lymphoblastic leukaemia antigen;    MES;    2-(morpholino)ethanesulfonic acid;    NEP;    neprilysin;   

DOI  :  10.1016/S0014-5793(97)00681-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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 non-mutated and mutated enzymes with dipeptide inhibitors and hydrolysis of the substrate [Leu⁵, Arg⁶]enkephalin in order to evaluate the contribution of the S₂′ 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 P₂′ residue of the substrate, (2) the S₂′ subsite is vast and can accommodate bulky side chains, and (3) Arg-102 restricts access to the S₂′ subsite to some side chains such as arginine.

【 授权许可】

Unknown