Solano F, Martinez-Liarte J H, Jiménez-Cervantes C, García-Borrón J C, Lozano J A
Dept. of Biochemistry & Molecular Biology, School of Medicine, University of Murcia, Spain.
Biochem Biophys Res Commun. 1994 Nov 15;204(3):1243-50. doi: 10.1006/bbrc.1994.2596.
Dopachrome tautomerase (DCT) catalyzes the conversion of L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid through the melanogenic biosynthetic pathway. This enzyme, also named TRP2, belongs to the family of the tyrosinase related proteins. The three members of the family contain two highly conserved metal-binding sites with three histidines on each. Tyrosinase has copper at its active site. It was assumed that although DCT might have copper in those metal binding sites, its active site could be related to other two putative iron-binding sites located in different positions. Based on apoDCT preparation with cyanide and reconstitution experiments, we propose that DCT have zinc instead of copper at the two metal-binding sites and that those sites actually correspond to the active site. The involvement of zinc, which cannot undergo redox reactions, accounts for the reaction that DCT catalyzes, a tautomerization versus the copper-mediated oxidations catalyzed by tyrosinase.
多巴色素互变异构酶(DCT)通过黑色素生物合成途径催化L - 多巴色素转化为5,6 - 二羟基吲哚 - 2 - 羧酸。这种酶也被称为TRP2,属于酪氨酸酶相关蛋白家族。该家族的三个成员包含两个高度保守的金属结合位点,每个位点有三个组氨酸。酪氨酸酶的活性位点含有铜。据推测,尽管DCT在那些金属结合位点可能含有铜,但其活性位点可能与位于不同位置的另外两个假定的铁结合位点有关。基于用氰化物制备脱辅基DCT并进行重组实验,我们提出DCT在两个金属结合位点含有锌而非铜,并且这些位点实际上对应于活性位点。不能进行氧化还原反应的锌的参与,解释了DCT催化的反应,即互变异构,而不是酪氨酸酶催化的铜介导的氧化反应。