New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins.
Tyrosinases are widely distributed in nature. They are copper-containing oxidases belonging to the type 3 copper protein family, together with catechol oxidases and haemocyanins. Tyrosinases are essential enzymes in melanin biosynthesis and therefore responsible for pigmentation of skin and hair in mammals, where two more enzymes, the tyrosinase-related proteins (Tyrps), participate in the pathway. The structure and catalytic mechanism of mammalian tyrosinases have been extensively studied but they are not completely understood because of the lack of information on the tertiary structure. The availability of crystallographic data of one plant catechol oxidase and one bacterial tyrosinase has improved the model of the three-dimensional structure of the active site of the enzyme. Furthermore, sequence comparison of tyrosinase and the Tyrps reveals that the three orthologue proteins share many key structural features, because of their common origin from an ancestral gene, although the specific residues responsible for their different catalytic capabilities have not been identified yet. This review summarizes our current knowledge of tyrosinase and Tyrps structure and function and describes the catalytic mechanism of tyrosinase and Dct/Tyrp2, which are better characterized.
Olivares
Concepcion
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Department of Biochemistry, Molecular Biology & Immunology, School of Medicine, University of Murcia, Espinardo, Spain.
Solano
Francisco
F
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D004156:Catechol Oxidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D007527:Isoenzymes; D008543:Melanins; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase