ANALYSIS OF MUTATIONS IN THE COPPER-B BINDING REGION ASSOCIATED WITH TYPE-I (TYROSINASE-RELATED) OCULOCUTANEOUS ALBINISM

被引:16
作者
OETTING, WS
KING, RA
机构
[1] UNIV MINNESOTA,DEPT PEDIAT,MINNEAPOLIS,MN 55455
[2] UNIV MINNESOTA,INST HUMAN GENET,MINNEAPOLIS,MN 55455
来源
PIGMENT CELL RESEARCH | 1992年 / 5卷 / 05期
关键词
COPPER BINDING; ALBINISM; TYROSINASE; MUTATION;
D O I
10.1111/j.1600-0749.1992.tb00549.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mutations of the tyrosinase gene are responsible for type I (tyrosinase-related) oculocutaneous albinism (OCA), an autosomal recessive genetic syndrome with a broad phenotypic spectrum. Mutant tyrosinase alleles can be associated with no melanin synthesis (I-A, tyrosinase-negative OCA), small to moderate amounts of melanin (I-B, yellow OCA) or unusual pigment patterns (I-TS, temperature-sensitive OCA). A total of 26 mutations of this gene have been described in type I OCA. Analysis of all known missense mutations (n = 17) shows that most cluster in three areas of the coding region. Two clusters involve the copper A or copper B binding sites and may disrupt the metal ion-protein interaction necessary for enzyme function and the third cluster is located in exon I. Computer modeling of the secondary structure of the copper binding regions based on homology with the known crystal structure of hemocyanin show that they both consist of two alpha helicies containing three histidine ligands that complex to a single copper atom. Mutations in the copper B binding region lie in the region between the two alpha helices that consists of a loop structure. These mutations may affect tyrosinase activity by either altering the position of the alpha helical domains and thus preventing proper copper binding to the histidine ligands, or affecting a catalytic or substrate binding site located between the two alpha helical domains.
引用
收藏
页码:274 / 278
页数:5
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