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首页> 外文期刊>Molecular and Cellular Biology >Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis.
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Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis.

机译：酵母和人3-羟基-3-甲基戊二酰辅酶A还原酶（固醇生物合成的限速酶）之间的结构和功能保守性。

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摘要

The pathway of sterol biosynthesis is highly conserved in all eucaryotic cells. We demonstrated structural and functional conservation of the rate-limiting enzyme of the mammalian pathway, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase), between the yeast Saccharomyces cerevisiae and humans. The amino acid sequence of the two yeast HMG-CoA reductase isozymes was deduced from DNA sequence analysis of the HMG1 and HMG2 genes. Extensive sequence similarity existed between the region of the mammalian enzyme encoding the active site and the corresponding region of the two yeast isozymes. Moreover, each of the yeast isozymes, like the mammalian enzyme, contained seven potential membrane-spanning domains in the NH2-terminal region of the protein. Expression of cDNA clones encoding either hamster or human HMG-CoA reductase rescued the viability of hmg1 hmg2 yeast cells lacking this enzyme. Thus, mammalian HMG-CoA reductase can provide sufficient catalytic function to replace both yeast isozymes in vivo. The availability of yeast cells whose growth depends on human HMG-CoA reductase may provide a microbial screen to identify new drugs that can modulate cholesterol biosynthesis.
机译：在所有的真核细胞中，固醇的生物合成途径都是高度保守的。我们展示了酵母途径和人类之间的哺乳动物途径的限速酶3-羟基-3-甲基-戊二酰辅酶A还原酶（HMG-CoA还原酶）的结构和功能保守性。从HMG1和HMG2基因的DNA序列分析推导了两种酵母HMG-CoA还原酶同工酶的氨基酸序列。在编码活性位点的哺乳动物酶区域与两种酵母同工酶的相应区域之间存在广泛的序列相似性。此外，每种酵母同工酶都像哺乳动物酶一样，在蛋白质的NH2末端区域含有七个潜在的跨膜结构域。编码仓鼠或人类HMG-CoA还原酶的cDNA克隆的表达挽救了缺乏该酶的hmg1 hmg2酵母细胞的活力。因此，哺乳动物HMG-CoA还原酶可提供足够的催化功能以在体内替代两种酵母同工酶。其生长依赖于人类HMG-CoA还原酶的酵母细胞的可用性可能提供微生物筛选，以鉴定可调节胆固醇生物合成的新药。

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