Complete amino acid sequence of rat brain hexokinase, deduced from the cloned cDNA, and proposed structure of a mammalian hexokinase.

Complete amino acid sequence of rat brain hexokinase, deduced from the cloned cDNA, and proposed structure of a mammalian hexokinase.
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DOI:
10.1073/pnas.86.8.2563
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发表时间:
1989-04
影响因子:
11.1
通讯作者:
D. A. Schwab;J. Wilson
D. A. Schwab;J. Wilson
中科院分区:
综合性期刊1区
文献类型:
--
作者:
D. A. Schwab;J. Wilson

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已从克隆的cDNA的核苷酸序列推导出大鼠脑己糖激酶I型同工酶的完整氨基酸序列。 5'非翻译区中91个碱基的核苷酸序列以及poly(A)序列之前的整个3'非翻译区的核苷酸序列也已确定。脑己糖激酶的 N 端和 C 端半部彼此之间以及与酵母己糖激酶显示出广泛的序列相似性。这些结果直接支持了以下观点:约100kDa的哺乳动物己糖激酶是通过编码与约50kDa的酵母酶类似的祖先己糖激酶的基因的复制和融合过程进化而来的。利用这种序列相似性来表明脑己糖激酶和酵母酶的 N 端和 C 端区域之间结构的基本相似性,通过融合酵母己糖激酶的两个分子,开发了哺乳动物己糖激酶的拟议结构,其结构先前已通过 X 射线晶体学研究确定。该模型的各种特征与脑酶结构的实验观察结果一致。
The complete amino acid sequence for the type I isozyme of hexokinase from rat brain has been deduced from the nucleotide sequence of cloned cDNA. The nucleotide sequence of 91 bases in the 5' untranslated region as well as that of the entire 3' untranslated region preceding the poly(A) sequence have also been determined. The N- and C-terminal halves of brain hexokinase show extensive sequence similarity to each other and to yeast hexokinase. These results provide direct support for the proposal that the mammalian hexokinases of approximately 100 kDa have evolved by a process of duplication and fusion of a gene encoding an ancestral hexokinase similar to the yeast enzyme of approximately 50 kDa. Taking this similarity in sequence to indicate basic similarity in structure between the N- and C-terminal regions of brain hexokinase and the yeast enzyme, a proposed structure for the mammalian hexokinase has been developed by fusing two molecules of yeast hexokinase, whose structure has previously been determined by x-ray crystallographic studies. Various features of the model are shown to be consistent with experimental observations bearing on the structure of the brain enzyme.