Structural insights into the regulation of aromatic amino acid hydroxylation
Structural insights into the regulation of aromatic amino acid hydroxylation
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DOI：
10.1016/j.sbi.2015.07.004
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发表时间：
2015-12-01
影响因子：
6.8
通讯作者：
Fitzpatrick, Paul F.
中科院分区：
文献类型：
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作者：
Fitzpatrick, Paul F.
芳香族氨基酸羟化酶苯丙氨酸羟化酶、酪氨酸羟化酶和色氨酸羟化酶是同源四聚体，每个亚基含有同源催化结构域和趋异调节结构域。酪氨酸羟化酶的调节结构域的溶液结构确定其含有类似于苯丙氨酸羟化酶中的核心ACT结构域。酪氨酸羟化酶的分离的调节结构域形成稳定的二聚体，而苯丙氨酸羟化酶的分离的调节结构域经历单体-二聚体平衡，苯丙氨酸稳定二聚体。这些溶液性质与两种酶的调节机制是一致的，因为苯丙氨酸羟化酶通过苯丙氨酸结合到变构位点而被激活，而酪氨酸羟化酶通过在活性位点中结合儿茶酚胺而被调节。
The aromatic amino acid hydroxylases phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase are homotetramers, with each subunit containing a homologous catalytic domain and a divergent regulatory domain. The solution structure of the regulatory domain of tyrosine hydroxylase establishes that it contains a core ACT domain similar to that in phenylalanine hydroxylase. The isolated regulatory domain of tyrosine hydroxylase forms a stable dimer, while that of phenylalanine hydroxylase undergoes a monomer-dinner equilibrium, with phenylalanine stabilizing the dimer. These solution properties are consistent with the regulatory mechanisms of the two enzymes, in that phenylalanine hydroxylase is activated by phenylalanine binding to an allosteric site, while tyrosine hydroxylase is regulated by binding of catecholamines in the active site.