TYR-179 AND LYS-183 ARE ESSENTIAL FOR ENZYMATIC-ACTIVITY OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE
TYR-179 AND LYS-183 ARE ESSENTIAL FOR ENZYMATIC-ACTIVITY OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE
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DOI：
10.1016/0006-291x(92)92373-6
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发表时间：
1992-10-15
影响因子：
3.1
通讯作者：
WHITE, PC
中科院分区：
文献类型：
--
作者：
OBEID, J;WHITE, PC
Tyr-179和Lys-183可能是11β-羟基类固醇脱氢酶中功能重要的残基，因为该酶氨基酸在“短链脱氢酶”家族的所有成员中是绝对保守的。我们修改这些残基的大鼠cDNA的定点突变和转染这些结构到CHO细胞。还研究了一个高度但不是绝对保守的残基，Asp-110。Tyr-179突变为Phe或Ser完全消除了酶活性（皮质酮和11-脱氢皮质酮的相互转化），Lys-183→Arg也是如此。Asp-110→Asn仅轻度影响活性。Tyr-179和Lys-183可能直接参与这类酶的催化功能。
Tyr-179 and Lys-183 are likely to be functionally important residues in 11β-hydroxysteroid dehydrogenase, as thease amino acids are absolutely conserved in all members of the “short chain dehydrogenase” family. We modified these residues by site-directed mutagenesis of rat cDNA and transfected these constructs into CHO cells. A highly but not absolutely conserved residue, Asp-110, was also studied. Mutation of Tyr-179 to Phe or Ser completely abolished enzymatic activity (interconversion of corticosterone and 11-dehydrocorticosterone), as did Lys-183→Arg. Asp-110→Asn affected activity only mildly. Tyr-179 and Lys-183 may be directly involved in the catalytic function of this class of enzymes.