Premium
Characterisation of neprilysin (EC 3.4.24.11) S 2 ′ subsite
Author(s) -
Dion Natalie,
Cohen Paul,
Crine Philippe,
Boileau Guy
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00681-9
Subject(s) - chemistry , endopeptidase , neprilysin , side chain , stereochemistry , dipeptide , residue (chemistry) , enzyme , oligopeptide , peptide , arginine , amino acid , hydrolysis , biochemistry , substrate (aquarium) , organic chemistry , biology , ecology , polymer
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 [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.