The aromatic amino acid hydroxylases.
The aromatic amino acid hydroxylases.
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DOI：
10.1002/9780470123201.ch6
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
P. Fitzpatrick
中科院分区：
文献类型：
--
作者：
P. Fitzpatrick
苯丙氨酸羟基酶、酪氨酸羟基酶和色氨酸羟基酶构成了依赖于蝶呤的芳香氨基酸羟基酶家族。每种酶使用分子氧和四氢蝶呤作为底物，催化其各自氨基酸底物的芳香族侧链的羟基化。最近的进展为这些酶的结构、机制和调控提供了深入的见解。真核酶是由同源催化结构域和离散调控结构域组成的同源异构体。通过结构研究和定点突变相结合的方法，已经确定了活性部位铁原子的配体以及参与底物结合的残基。对非生理性和同位素取代底物的机理研究已经提供了羟化机理的详细信息。虽然苯丙氨酸和酪氨酸羟基酶的复杂调控性质仍不完全清楚，但调控对关键动力学参数的影响已经被识别。苯丙氨酸羟基酶受底物的磷酸化和变构调节之间的相互作用调节。酪氨酸羟化酶受磷酸化和儿茶酚胺反馈抑制的调节。
The enzymes phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase constitute the family of pterin-dependent aromatic amino acid hydroxylases. Each enzyme catalyzes the hydroxylation of the aromatic side chain of its respective amino acid substrate using molecular oxygen and a tetrahydropterin as substrates. Recent advances have provided insights into the structures, mechanisms, and regulation of these enzymes. The eukaryotic enzymes are homotetramers comprised of homologous catalytic domains and discrete regulatory domains. The ligands to the active site iron atom as well as residues involved in substrate binding have been identified from a combination of structural studies and site-directed mutagenesis. Mechanistic studies with nonphysiological and isotopically substituted substrates have provided details of the mechanism of hydroxylation. While the complex regulatory properties of phenylalanine and tyrosine hydroxylase are still not fully understood, effects of regulation on key kinetic parameters have been identified. Phenylalanine hydroxylase is regulated by an interaction between phosphorylation and allosteric regulation by substrates. Tyrosine hydroxylase is regulated by phosphorylation and feedback inhibition by catecholamines.