Inactivation of dopamine beta-hydroxylase by p-cresol: evidence for a second, minor site of covalent modification at tyrosine 357.
p-Cresol is a mechanism-based inhibitor of bovine dopamine beta-hydroxylase (3,4-dihydroxyphenethylamine, ascorbate: oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1) (DBH) which covalently modifies a tyrosine at position 216 during inactivation (DeWolf, W.E., Jr., Carr, S.A., Varrichio, A., Goodhart, P.J., Mentzer, M.A., Roberts, G.D., Southan, C., Dolle, R.E. and Kruse, L.I. (1988) Biochemistry 27, 9093-9101). Here we report the recovery and characterization of additional minor peptides that are produced during the inactivation of DBH with p-[3H]cresol. Sequence and structural analysis of these peptides indicates tyrosine 357 as a second, minor site of modification.
Southan
C
C
Department of Medicinal Chemistry, Smith Kline & French Research Limited, Welwyn, U.K.
DeWolf
W E
WE
Kruse
L I
LI
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003408:Cresols / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis; D012689:Sequence Homology, Nucleic Acid; D014357:Trypsin; D014443:Tyrosine
D003408:Cresols; D010446:Peptide Fragments; C032538:4-cresol; D014443:Tyrosine; D004299:Dopamine beta-Hydroxylase; D014357:Trypsin