title: The irreversible inactivation of two copper-dependent monooxygenases by sulfite: peptidylglycine alpha-amidating enzyme and dopamine beta-monooxygenase.
abstract: Peptidylglycine alpha-amidating enzyme (alpha-AE) and dopamine beta-monooxygenase (D beta M), two copper-dependent monooxygenases that have catalytic and structural similarities, are irreversibly inactivated by sodium sulfite in a time- and concentration-dependent manner. Studies with alpha-AE show that the sulfite-mediated inactivation is dependent on the presence of redox active transition metals free in solution, with Cu(II) being the most effective in supporting the inactivation reaction. Sulfite inactivation of alpha-AE is specific for the monooxygenase reaction of this bifunctional enzyme and amidated peptides provide protection against the inactivation. Consequently, the sulfite-mediated inactivation of alpha-AE and D beta M most likely results from the transition metal-catalyzed oxidation of sulfite to the sulfite radical, SO3-.
authors.affiliation: Analytical Protein and Organic Chemistry Group, Unigene Laboratories, Inc., Fairfield, NJ 07004, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Merkler
authors.forename: R
authors.initials: R
authors.lastname: Kulathila
authors.forename: W A
authors.initials: WA
authors.lastname: Francisco
authors.forename: D E
authors.initials: DE
authors.lastname: Ash
authors.forename: J
authors.initials: J
authors.lastname: Bell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D003300:Copper / Q000494:pharmacology*; D006224:Cricetinae; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation / Q000187:drug effects; D005609:Free Radicals; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors; D013373:Substance P / Q000494:pharmacology; D013447:Sulfites / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000201:enzymology
chemical_list: D005609:Free Radicals; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D013447:Sulfites; D013373:Substance P; D003300:Copper; D006899:Mixed Function Oxygenases; D004299:Dopamine beta-Hydroxylase; C035189:peptidylglycine monooxygenase; C025026:sodium sulfite