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首页> 外文期刊>Molecular and Cellular Biology >Conservation between human and fungal squalene synthetases: similarities in structure, function, and regulation.
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Conservation between human and fungal squalene synthetases: similarities in structure, function, and regulation.

机译：人和角鲨烯合成酶之间的保守性：结构，功能和调控的相似性。

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Squalene synthetase (farnesyl diphosphate:farnesyl diphosphate farnesyltransferase; EC 2.5.1.21) is thought to represent a major control point of isoprene and sterol biosynthesis in eukaryotes. We demonstrate structural and functional conservation between the enzymes from humans, a budding yeast (Saccharomyces cerevisiae), and a fission yeast (Schizosaccharomyces pombe). The amino acid sequences of the human and S. pombe proteins deduced from cloned cDNAs were compared to those of the known S. cerevisiae protein. All are predicted to encode C-terminal membrane-spanning proteins of approximately 50 kDa with similar hydropathy profiles. Extensive sequence conservation exists in regions of the enzyme proposed to interact with its prenyl substrates (i.e., two farnesyl diphosphate molecules). Many of the highly conserved regions are also present in phytoene and prephytoene diphosphate synthetases, enzymes which catalyze prenyl substrate condensation reactions analogous to that of squalene synthetase. Expression of cDNA clones encoding S. pombe or hybrid human-S. cerevisiae squalene synthetases reversed the ergosterol requirement of S. cerevisiae cells bearing ERG9 gene disruptions, showing that these enzymes can functionally replace the S. cerevisiae enzyme. Inhibition of sterol synthesis in S. cerevisiae and S. pombe cells or in cultured human fibroblasts by treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor lovastatin resulted in elevated levels of squalene synthetase mRNA in all three cell types.
机译：角鲨烯合成酶（法呢基二磷酸：法呢基二磷酸法呢基转移酶; EC 2.5.1.21）被认为是真核生物中异戊二烯和固醇生物合成的主要控制点。我们展示了人类，发芽酵母（酿酒酵母）和裂变酵母（裂殖酵母）之间的酶之间的结构和功能保守。从克隆的cDNA推导出的人和粟酒裂殖酵母蛋白质的氨基酸序列与已知的酿酒酵母蛋白质进行比较。预计所有这些都编码具有相似亲水性分布的约50 kDa的C端跨膜蛋白。提议的与其异戊二烯基底物相互作用的区域（即两个法呢基二磷酸分子）存在广泛的序列保守性。六氢番茄红素和四氢番茄红素前磷酸二氢酯合成酶中也存在许多高度保守的区域，这些酶催化异戊二烯底物缩合反应类似于角鲨烯合成酶。编码粟酒裂殖酵母或杂种人S的cDNA克隆的表达。酿酒角鲨烯合成酶逆转了带有ERG9基因破坏的酿酒酵母细胞的麦角固醇需求，表明这些酶可以在功能上替代酿酒酵母酶。通过用3-羟基-3-甲基戊二酰辅酶A处理，在酿酒酵母和粟酒裂殖酵母细胞中或在培养的人成纤维细胞中抑制甾醇合成会导致在所有三种细胞类型中角鲨烯合成酶mRNA的水平升高。

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