Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis
Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis
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DOI：
10.1074/jbc.m212124200
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发表时间：
2003-03-07
影响因子：
4.8
通讯作者：
Sacchettini, JC
中科院分区：
文献类型：
--
作者：
Cho, Y;Sharma, V;Sacchettini, JC
N-1-（5 '-磷酸核糖基）-ATP转移酶催化组氨酸生物合成途径的第一步，并通过产物组氨酸的反馈机制进行调节。来自结核分枝杆菌的N-1-（5 ′-磷酸核糖基）-ATP转移酶与抑制剂组氨酸和AMP复合物的晶体结构已被确定为1.8埃分辨率，而没有配体时为2.7埃分辨率。活性酶主要以二聚体形式存在，组氨酸抑制形式为六聚体。该结构代表了磷酸核糖基转移酶的新折叠，由三个连续结构域组成。抑制剂AMP结合在两个催化结构域之间形成的活性位点空腔中。已从AMP：His结合和载脂蛋白结构之间的构象差异推导出变构抑制机制的模型。
The N-1-(5'-phosphoribosyl)-ATP transferase catalyzes the first step of the histidine biosynthetic pathway and is regulated by a feedback mechanism by the product histidine. The crystal structures of the N-1-(5'-phosphoribosyl)-ATP transferase from Mycobacterium tuberculosis in complex with inhibitor histidine and AMP has been determined to 1.8 Angstrom resolution and without ligands to 2.7 Angstrom resolution. The active enzyme exists primarily as a dimer, and the histidine-inhibited form is a hexamer. The structure represents a new fold for a phosphoribosyltransferase, consisting of three continuous domains. The inhibitor AMP binds in the active site cavity formed between the two catalytic domains. A model for the mechanism of allosteric inhibition has been derived from conformational differences between the AMP:His-bound and apo structures.