通过细胞色素P450 17α-羟化酶（CYP17）的精氨酸347和精氨酸358与细胞色素b5的相互作用来控制人体内雄激素的生物合成。
Control of androgen biosynthesis in the human through the interaction of Arg347 and Arg358 of CYP17 with cytochrome b5.
作者信息
Lee-Robichaud P, Akhtar M E, Akhtar M
机构信息
Department of Biochemistry, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
出版信息
Biochem J. 1998 Jun 1;332 ( Pt 2)(Pt 2):293-6. doi: 10.1042/bj3320293.
Abstract
The lyase activity of human CYP17 (17alpha-hydroxylase-17,20-lyase also P-450c17 or P-45017alpha) is greatly dependent on the presence of cytochrome b5, and this effect has been ascribed an important regulatory role [Lee-Robichaud, Wright, Akhtar and Akhtar (1995) Biochem. J. 308, 901-908]. This facet was further investigated by site-directed mutagenesis of selected basic residues of human CYP17. The purified mutant proteins were subjected to detailed kinetic analysis. It was found that the mutation of Lys83, Arg347 and Arg358 produced proteins that were deficient in their responsiveness to cytochrome b5, and the effect was most pronounced for the two arginine mutants (Arg347-->His and Arg358-->Gln) which have been found in male patients suffering from genital ambiguity. These residues are invoked to mediate protein-protein interaction between cytochrome b5 and CYP17, which 'awakens' the lyase activity of the enzyme required for androgen formation.
摘要
人细胞色素P450 17α（17α-羟化酶-17,20-裂解酶，也称为P-450c17或P-45017α）的裂解酶活性很大程度上依赖于细胞色素b5的存在，并且这种作用被认为具有重要的调节作用[Lee-Robichaud、Wright、Akhtar和Akhtar（1995年）《生物化学杂志》308卷，901 - 908页]。通过对人细胞色素P450 17α的选定碱性残基进行定点诱变，对这一方面进行了进一步研究。对纯化的突变蛋白进行了详细的动力学分析。发现赖氨酸83、精氨酸347和精氨酸358的突变产生的蛋白对细胞色素b5的反应性不足，对于在患有生殖器模糊的男性患者中发现的两个精氨酸突变体（精氨酸347→组氨酸和精氨酸358→谷氨酰胺），这种影响最为明显。这些残基被认为介导细胞色素b5与细胞色素P450 17α之间的蛋白质-蛋白质相互作用，从而“激活”雄激素形成所需酶的裂解酶活性。
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