Zinc plays a key role in human and bacterial GTP cyclohydrolase I
Zinc plays a key role in human and bacterial GTP cyclohydrolase I
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DOI：
10.1073/pnas.240463497
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发表时间：
2000-12-05
影响因子：
11.1
通讯作者：
Bacher, A
中科院分区：
文献类型：
--
作者：
Auerbach, G;Herrmann, A;Bacher, A
以大肠杆菌酶的坐标为模型，用Patterson搜索法求解了重组人GTP环水解酶I的晶体结构。人类和细菌的酶被证明含有一个与His侧链配位的必需锌离子，以及在早期对大肠杆菌酶的研究中逃脱检测的同十聚体酶的每个活性位置上的两个硫醇基团。锌离子被认为是为底物GTP的8个咪唑环碳原子的攻击而产生的羟基亲核剂，它还可能参与中间体2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5‘-三磷酸的甲酸盐的水解释放，以及核糖部分的连续Amadori重排。
The crystal structure of recombinant human GTP cyclohydrolase I was solved by Patterson search methods by using the coordinates of the Escherichia coli enzyme as a model. The human as well as bacterial enzyme were shown to contain an essential zinc ion coordinated to a His side chain and two thiol groups in each active site of the homodecameric enzymes that had escaped detection during earlier studies of the E. coli enzyme. The zinc ion is proposed to generate a hydroxyl nucleophile for attack of imidazole ring carbon atom eight of the substrate, GTP, It may also be involved in the hydrolytic release of formate from the intermediate, 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate, and in the consecutive Amadori rearrangement of the ribosyl moiety.