Atrial dipeptidyl carboxyhydrolase is a zinc-metallo proteinase which possesses tripeptidyl carboxyhydrolase activity.
Atrial dipeptidyl carboxyhydrolase readily converts one atrial natriuretic peptide, atriopeptin II (Ser103-Arg125 peptide), to another, atriopeptin I (Ser103-Ser123 peptide), by selective removal of the C-terminal dipeptide, Phe-Arg. The atrial peptides possess natriuretic, diuretic, smooth muscle relaxant, and cardiodynamic properties and their existence has shown the mammalian heart to be an endocrine organ. After inactivating the bovine atrial enzyme with EDTA, activity is restored by the addition of Co+2, Zn+2 and Mn+2 but not by Cu+2, Mg+2, Ca+2, or Cd+2. The enzyme is thus likely to be a zinc-metallo proteinase. In addition to its dipeptidyl activity, the enzyme also displays tripeptidyl carboxyhydrolase activity with atriopeptin III (Ser103-Try126 peptide) as substrate. The hydrolytic products resulting from tripeptidyl cleavage are atriopeptin I and Phe-Arg-Tyr. However, with [mercaptopropionyl105,(D)Ala107]-atriopeptin III-NH2 peptide (a potent agonist of atriopeptin III) as substrate, the enzyme acts exclusively as a tripeptidyl carboxyhydrolase. To examine the basis for this shift in cleavage point, pentapeptides based on the C-terminal sequence of atriopeptin III were prepared; a C-terminal Tyr or Tyr-NH2 residue is not sufficient to cause the change in cleavage point. The amidated pentapeptide is not a substrate but is a competitive inhibitor of hydrolysis of the corresponding free-acid peptide.
Soler
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DF
Virginia Commonwealth University, Department of Biochemistry and Molecular Biophysics, Richmond 23298.
Harris
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RB
D000818:Animals; D002413:Cations, Divalent; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004492:Edetic Acid / Q000494:pharmacology; D010450:Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D006325:Heart Atria / Q000201:enzymology; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D009842:Oligopeptides / Q000138:chemical synthesis; D051381:Rats; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity
D002413:Cations, Divalent; D009842:Oligopeptides; D004492:Edetic Acid; D010450:Endopeptidases; C046971:atrial dipeptidyl carboxyhydrolase