Chromogranin A can act as a reversible processing enzyme inhibitor. Evidence from the inhibition of the IRCM-serine protease 1 cleavage of pro-enkephalin and ACTH at pairs of basic amino acids.
Bovine parathyroid chromogranin A inhibits the cleavage of Z-Ala-Lys-Arg-AMC by either trypsin or IRCM-serine protease 1 (IRCM-SP1), a putative novel processing enzyme originally isolated from porcine pituitary anterior and neurointermediate lobes. On larger substrates, chromogranin A is a reversible competitive inhibitor of the cleavage at pairs of basic amino acids by IRCM-SP1. The substrates tested included pituitary ACTH and adrenal medulla pro-enkephalin-derived peptides such as the 8.6 kDa synenkephalin-containing precursor and peptide B. Chromogranin A is itself selectively processed by IRCM-SP1, and ACTH was shown to compete for such cleavage. These data suggest that chromogranins as a class of acidic proteins could participate in the tissue-specific processing of pro-hormones.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D002837:Chromaffin Granules / Q000378:metabolism; D053379:Chromogranin A; D002864:Chromogranins / Q000494:pharmacology*; D010450:Endopeptidases / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D011480:Protease Inhibitors; D011498:Protein Precursors / Q000378:metabolism; D012697:Serine Endopeptidases
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D004745:Enkephalins; D009419:Nerve Tissue Proteins; D011480:Protease Inhibitors; D011498:Protein Precursors; C029992:proenkephalin; D000324:Adrenocorticotropic Hormone; D010450:Endopeptidases; C048880:IRCM-serine protease 1; D012697:Serine Endopeptidases