Structural studies of the catalytic reaction pathway of a hyperthermophilic histidinol-phosphate aminotransferase
Structural studies of the catalytic reaction pathway of a hyperthermophilic histidinol-phosphate aminotransferase
复制标题
DOI：
10.1074/jbc.m400291200
复制
发表时间：
2004-05-14
影响因子：
4.8
通讯作者：
Wilmanns, M
中科院分区：
文献类型：
--
作者：
Fernandez, FJ;Vega, MC;Wilmanns, M
在组氨酸生物合成中，组氨醇磷酸氨基转移酶催化氨基从谷氨酸转移到咪唑丙二醇磷酸酯，产生2-氧戊二酸和组二醇磷酸。在一些生物中，如嗜热性极强的嗜热菌Thermotoga maritima，到目前为止还没有鉴定出特定的酪氨酸和芳香族氨基酸转氨酶，这表明组氨醇-磷酸转氨酶在其他产生芳香族氨基酸的转氨化反应中还有另外的作用。为了深入了解这种转氨酶的特殊功能，我们测定了它的晶体结构，在没有磷酸以外的任何配体的情况下，在共价结合的5‘-磷酸吡哆醛存在的情况下，在辅酶磷酸组氨酸加合物和5’-磷酸吡哆胺存在的情况下测定了它的晶体结构。该酶接受磷酸组氨酸、酪氨酸、色氨酸和苯丙氨酸作为底物，但不接受组氨酸。这些结构提供了一个模型，说明这些不同的底物如何被组氨醇-磷酸转氨酶调节。与来自不同生物的组氨醇-磷酸氨基转移酶相比，该酶的一些结构特征在毛滴虫酶和来自鼠伤寒沙门氏菌的相关苏氨酸-磷酸脱羧酶之间保存得更好。
In histidine biosynthesis, histidinol-phosphate aminotransferase catalyzes the transfer of the amino group from glutamate to imidazole acetol-phosphate producing 2-oxoglutarate and histidinol phosphate. In some organisms such as the hyperthermophile Thermotoga maritima, specific tyrosine and aromatic amino acid transaminases have not been identified to date, suggesting an additional role for histidinol-phosphate aminotransferase in other transamination reactions generating aromatic amino acids. To gain insight into the specific function of this transaminase, we have determined its crystal structure in the absence of any ligand except phosphate, in the presence of covalently bound pyridoxal 5'-phosphate, of the coenzyme histidinol phosphate adduct, and of pyridoxamine 5'-phosphate. The enzyme accepts histidinol phosphate, tyrosine, tryptophan, and phenylalanine, but not histidine, as substrates. The structures provide a model of how these different substrates could be accommodated by histidinol-phosphate aminotransferase. Some of the structural features of the enzyme are more preserved between the T. maritima enzyme and a related threonine-phosphate decarboxylase from S. typhimurium than with histidinol-phosphate aminotransferases from different organisms.