Mapping sequence differences between thimet oligopeptidase and neurolysin implicates key residues in substrate recognition.

ABSTRACT: The highly homologous endopeptidases thimet oligopeptidase and neurolysin are both restricted to short peptide substrates and share many of the same cleavage sites on bioactive and synthetic peptides. They sometimes target different sites on the same peptide, however, and defining the determinants of differential recognition will help us to understand how both enzymes specifically target a wide variety of cleavage site sequences. We have mapped the positions of the 224 surface residues that differ in sequence between the two enzymes onto the surface of the neurolysin crystal structure. Although the deep active site channel accounts for about one quarter of the total surface area, only 11% of the residue differences map to this region. Four isolated sequence changes (R470/E469, R491/M490, N

SUBMITTER: Ray K 

PROVIDER: S-EPMC2373592 | biostudies-literature | 2002 Sep

REPOSITORIES: biostudies-literature