Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation.
Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation.
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DOI：
10.1016/s0021-9258(17)39242-6
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发表时间：
1985-08
期刊：
影响因子：
--
通讯作者：
Kenneth L. Luskeyg;Bryn Stevens
中科院分区：
文献类型：
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作者：
Kenneth L. Luskeyg;Bryn Stevens
人3-羟基-3-甲基戊二酰辅酶A还原酶（调节胆固醇合成的膜结合糖蛋白）的全长cDNA从人胎儿肾上腺cDNA文库中分离。该cDNA的核苷酸序列显示，人还原酶长888个氨基酸，与仓鼠酶具有高度同源性。氨基端膜结合结构域是两个物种之间最保守的区域（339个氨基酸中有7个取代）。该区域，预计跨越内质网膜7倍，介导的甾醇存在下的还原酶的加速降解。羧基末端催化结构域也是高度保守的（439个氨基酸中有22个取代）。然而，这两个结构域之间的接头区域已经分叉（110个氨基酸中的32个取代）。HMG-CoA还原酶中膜结合结构域的保守性支持了以下假设：甾醇调节的降解是抑制还原酶活性和调节人类以及仓鼠胆固醇代谢的重要机制。
A full length cDNA for human 3-hydroxy-3-methylglutaryl coenzyme A reductase, the membrane-bound glycoprotein that regulates cholesterol synthesis, was isolated from a human fetal adrenal cDNA library. The nucleotide sequence of this cDNA shows that the human reductase is 888 amino acids long and shares a high degree of homology with the hamster enzyme. The amino-terminal membrane-bound domain is the most conserved region between the two species (7 substitutions out of 339 amino acids). This region, which is predicted to span the endoplasmic reticulum membrane seven times, mediates accelerated degradation of reductase in the presence of sterols. The carboxyl-terminal catalytic domain is also highly conserved (22 substitutions out of 439 amino acids). However, the linker region between these two domains has diverged (32 substitutions out of 110 amino acids). Conservation of the structure of the membrane-bound domain in HMG-CoA reductase supports the hypothesis that sterol-regulated degradation is an important mechanism for suppression of reductase activity and for regulation of cholesterol metabolism in humans as well as in hamsters.