Structure and mechanism of yeast RNA triphosphatase: An essential component of the mRNA capping apparatus
Structure and mechanism of yeast RNA triphosphatase: An essential component of the mRNA capping apparatus
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DOI：
10.1016/s0092-8674(00)81541-x
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发表时间：
1999-11-24
期刊：
影响因子：
64.5
通讯作者：
Shuman, S
中科院分区：
文献类型：
--
作者：
Lima, CD;Wang, LK;Shuman, S
RNA三磷酸酶是一种必需的mRNA加工酶，催化帽形成的第一步。酵母RNA三磷酸酶Cet1p的2.05埃晶体结构揭示了一种新的活性位点折叠，由此八链β桶形成拓扑封闭的三磷酸隧道。隧道中心的硫酸盐与二价阳离子和伸入隧道的碱性氨基酸的相互作用表明了突变数据所支持的催化机制。离散的表面结构域介导Cet1p同二聚化和Cet1p结合到加帽装置的鸟苷酰转移酶组分。真菌RNA三磷酸酶的结构和机制与哺乳动物mRNA加帽酶完全不同。因此，RNA三磷酸酶为基于结构的抗真菌药物发现提供了理想的靶标。
RNA triphosphatase is an essential mRNA processing enzyme that catalyzes the first step in cap formation. The 2.05 Angstrom crystal structure of yeast RNA triphosphatase Cet1p reveals a novel active site fold whereby an eight-stranded beta barrel forms a topologically closed triphosphate tunnel. Interactions of a sulfate in the center of the tunnel with a divalent cation and basic amino acids projecting into the tunnel suggest a catalytic mechanism that is supported by mutational data. Discrete surface domains mediate Cet1p homodimerization and Cet1p binding to the guanylyltransferase component of the capping apparatus. The structure and mechanism of fungal RNA triphosphatases are completely different from those of mammalian mRNA capping enzymes. Hence, RNA triphosphatase presents an ideal target for structure-based antifungal drug discovery.