Tyrosinase-catalyzed binding of 3,4-dihydroxyphenylalanine with proteins through the sulfhydryl group.
The cytotoxicity of catechols has been ascribed to covalent binding of the omicron-quinone oxidation products to proteins through sulfhydryl groups. The nature of the covalent binding was studied with dopaquinone formed on tyrosinase oxidation of 3,4-dihydroxyphenylalanine (DOPA). After acid hydrolysis of the reaction products, cysteinyldopas liberated (protein-bound cysteinyldopas) were determined by HPLC with electrochemical detection. When 0.1 mM DOPA was oxidized in the presence of 0.2 mM bovine serum albumin, alcohol dehydrogenase or isocitrate dehydrogenase, protein-bound cysteinyldopas were formed in yields of 5.4, 44, or 33%, respectively. The covalent binding was almost completely inhibited by 1 mM cysteine or 1 mM ascorbic acid, but 10 mM lysine had no effect. These results unambiguously demonstrate that dopaquinone can bind with proteins mostly through sulfhydryl groups.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D001487:Basidiomycota / Q000201:enzymology; D001665:Binding Sites; D004156:Catechol Oxidase / Q000378:metabolism*; D003545:Cysteine; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013438:Sulfhydryl Compounds
D013438:Sulfhydryl Compounds; D004295:Dihydroxyphenylalanine; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D007521:Isocitrate Dehydrogenase; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D003545:Cysteine