FULL-LENGTH CDNA FOR RABBIT TRYPTOPHAN-HYDROXYLASE - FUNCTIONAL DOMAINS AND EVOLUTION OF AROMATIC AMINO-ACID HYDROXYLASES
FULL-LENGTH CDNA FOR RABBIT TRYPTOPHAN-HYDROXYLASE - FUNCTIONAL DOMAINS AND EVOLUTION OF AROMATIC AMINO-ACID HYDROXYLASES
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DOI：
10.1073/pnas.84.16.5530
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发表时间：
1987-08-01
影响因子：
11.1
通讯作者：
WOO, SLC
中科院分区：
文献类型：
--
作者：
GRENETT, HE;LEDLEY, FD;WOO, SLC
用抗大鼠苯丙氨酸羟化酶的抗体筛选表达文库，从兔松果体中克隆到色氨酸羟化酶的全长cDNA。产生免疫反应性物质的克隆含有与苯丙氨酸羟化酶同源但不同的序列。家兔松果体和脑干的cDNA与mRNA杂交，而肝脏的cDNA与mRNA不杂交。兔色氨酸羟化酶序列与苯丙氨酸羟化酶和酪氨酸羟化酶序列的比较表明，这三个生物蝶呤依赖的芳香族氨基酸羟化酶是高度同源的，反映了一个共同的进化起源从一个单一的原始遗传位点。序列同源性的模式支持的假设，羧基末端的三分之二的分子构成的酶活性的核心，和氨基末端的三分之一的分子构成底物特异性域。
A full-length cDNA for tryptophan hydroxylase was cloned from rabbit pineal body by screening an expression library with antibody against rat phenylalanine hydroxylase, which crossreacts with rabbit tryptophan hydroxylase. Clones producing immunoreactive material contain sequences homologous to, yet distinct from, phenylalanine hydroxylase. The rabbit cDNA hybridizes to mRNA in pineal body and brainstem but not in liver. Comparison of the rabbit tryptophan hydroxylase sequence with the sequences of phenylalanine hydroxylase and tyrosine hydroxylase demonstrates that these three biopterin-dependent aromatic amino acid hydroxylases are highly homologous, reflecting a common evolutionary origin from a single primordial genetic locus. The pattern of sequence homology supports the hypothesis that the carboxyl-terminal two-thirds of the molecules constitute the enzymatic activity cores, and the amino-terminal thirds of the molecules constitute domains for substrate specificity.