Premium
Unique cleavage specificity of ‘prohormone thiol protease’ related to proenkephalin processing
Author(s) -
Azaryan Anahit V.,
Hook Vivian Y.H.
Publication year - 1994
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 - 10.1016/0014-5793(94)80456-7
Subject(s) - chemistry , proenkephalin , prohormone , biochemistry , monobasic acid , cleavage (geology) , cysteine , peptide , scissile bond , proteases , prohormone convertase , cysteine protease , stereochemistry , enzyme , protease , exopeptidase , enkephalin , biology , paleontology , receptor , fracture (geology) , opioid , hormone , polymer chemistry
‘Prohormone thiol protease’ (PTP) represents the major enkephalin precursor processing activity in chromaffin granules. In this study, cleavage specificity of PTP for paired basic and monobasic residues was examined with a series of model peptide‐MCA (‐methylcoumarinamide) substrates. Monobasic peptides were cleaved at the COOH‐ and NH 2 ‐terminal sides of the single basic residue. Dibasic peptides, however, were preferentially cleaved at the NH 2 ‐terminal side of the pair, or between the two basic residues, with low cleavage at the COOH‐terminal side of the pair. Inhibition by the peptide inhibitor ( d ‐Tyr)‐Glu‐Phe‐Lys‐Arg‐CH 2 Cl provided further evidence for ptp's specificity for the dibasic Lys‐Arg site. Inhibition by Z‐Leu‐Val‐Gly‐CHN 2 ; and Z‐Arg‐Leu‐Val‐Gly‐CHN 2 ; suggests involvement of Val‐Gly in substrate binding to PTP; these two cystatin C‐related inhibitors also indicate PTP as a cysteine protease. These results demonstrate PTP's unique cleavage specificity that differs from other processing endopeptidases, including the subtilisin‐related proprotein convertases, PC1/PC3, and PC2, as well as the pituitary proopiomelanocortin‐converting enzyme, PCE. This study provides further evidence for PTP as a novel prohormone processing enzyme that belongs to the class of cysteine proteases.