Oetting W S, King R A
Department of Medicine, University of Minnesota, Minneapolis 55455.
Pigment Cell Res. 1994 Oct;7(5):285-90. doi: 10.1111/j.1600-0749.1994.tb00629.x.
Mutations of the tyrosinase gene associated with a partial or complete loss of enzymatic activity are responsible for tyrosinase related oculocutaneous albinism (OCA1). A large number of mutations have been identified and their analysis has provided insight into the biology of tyrosinase and the pathogenesis of these different mutations. Missense mutations produce their effect on the activity of an enzyme by altering an amino acid at a specific site. The location of these mutations in the peptide can be used to indicate potential domains important for enzymatic activity. Missense mutations of the tyrosinase polypeptide cluster in four regions, suggesting that these are important functional domains. Two of the potential domains involve the copper binding sites while the others are likely involved in substrate binding. More critical analysis of the copper binding domain of tyrosinase can be gained by analyzing the structure of hemocyanin, a copper-binding protein with a high degree of homology to tyrosinase in the copper binding region. This analysis indicates a single catalytic site in tyrosinase for all enzymatic activities.
与酶活性部分或完全丧失相关的酪氨酸酶基因突变是导致酪氨酸酶相关眼皮肤白化病（OCA1）的原因。已经鉴定出大量突变，对它们的分析为了解酪氨酸酶的生物学特性和这些不同突变的发病机制提供了线索。错义突变通过改变特定位点的氨基酸来对酶的活性产生影响。这些突变在肽中的位置可用于指示对酶活性重要的潜在结构域。酪氨酸酶多肽的错义突变集中在四个区域，表明这些是重要的功能结构域。其中两个潜在结构域涉及铜结合位点，而其他结构域可能参与底物结合。通过分析血蓝蛋白的结构可以对酪氨酸酶的铜结合结构域进行更关键的分析，血蓝蛋白是一种在铜结合区域与酪氨酸酶具有高度同源性的铜结合蛋白。该分析表明酪氨酸酶中所有酶活性都有一个单一的催化位点。
