Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.17 (PCE)
 1,301 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pro-opiomelanocortin (adrenocorticotropin/endorphin prohormone) is processed to yield active hormones by cleavages at paired basic amino acid residues. In this study, an enzyme that specifically cleaves at the paired basic residues of this prohormone has been purified from bovine pituitary intermediate lobe secretory vesicles, the intracellular processing site of proopiomelanocortin. This enzyme, named pro-opiomelanocortin converting enzyme, has been characterized as a glycoprotein of Mr approximately 70,000. It has an apparent isoelectric point between 3.5 and 4.0. The pH optimum of the pro-opiomelanocortin converting enzyme is between 4 and 5, but the enzyme is highly active at the intravesicular pH of 5.1-5.6. The enzyme specifically cleaved the Lys-Arg pairs of pro-opiomelanocortin to yield Mr = to 21,000-23,000 ACTH, beta-lipotropin, Mr 13,000 and 4,500 ACTH, beta-endorphin, and a Mr = 16,000 NH2-terminal glycopeptide, the products synthesized by the pituitary intermediate lobe in situ. NH2- and COOH-terminal analysis of the products indicated that the pro-opiomelanocortin converting enzyme cleaves the peptide bond either between the Lys and Arg or on the carboxyl side of the Arg at Lys-Arg pairs of pro-opiomelanocortin. The intracellular localization, pH optimum, and cleavage specificity of the enzyme suggest that it may function as a pro-opiomelanocortin processing enzyme in the pituitary intermediate lobe in vivo.
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PMID:Purification and characterization of a paired basic residue-specific pro-opiomelanocortin converting enzyme from bovine pituitary intermediate lobe secretory vesicles. 298 47

'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 NH2-terminal sides of the single basic residue. Dibasic peptides, however, were preferentially cleaved at the NH2-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-CH2Cl provided further evidence for PTP's specificity for the dibasic Lys-Arg site. Inhibition by Z-Leu-Val-Gly-CHN2 and Z-Arg-Leu-Val-Gly-CHN2 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.
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PMID:Unique cleavage specificity of 'prohormone thiol protease' related to proenkephalin processing. 813 39