小说具体嘌呤核苷水解酶的结构和功能,从锥虫属间日疟原虫。
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诗W, Decanniere K,皮尔R,所J,布洛E,帕金DW, Steyaert J
小说具体嘌呤核苷水解酶的结构和功能,从锥虫属间日疟原虫。
J杂志。2001年4月13日,307 (5):1363 - 79。
- PubMed ID
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11292348 (在PubMed]
- 文摘
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寄生原生动物的嘌呤救助途径是目前被认为是药物开发的一个目标,因为这些生物不能合成嘌呤新创。了解相关酶的结构和机制有助于发展的强有力的抑制剂,导致新的治疗药物。嘌呤核苷水解酶是关键酶的救助途径锥虫科,他们尤其有吸引力,因为他们没有在哺乳动物细胞。我们克隆、表达和纯化锥虫属间日疟原虫的核苷水解酶。衬底活动概要文件建立的酶属于inosine-adenosine-guanosine-preferring核苷水解酶(IAG-NH)。我们解决了酶的晶体结构为1.6使用疯狂技术解决。酶与底物的复杂模拟3-deaza-adenosine。这是第一个IAG-NH文献中报道的结构。t .间日疟IAG-NH是为,每个亚基组成的十beta-strands 12阿尔法螺旋和三个小3(10)螺旋。中央六的八链β褶板形成一个主题类似于罗斯曼褶皱。 Superposition of the active sites of this IAG-NH and the inosine-uridine-preferring nucleoside hydrolase (IU-NH) of Crithidia fasciculata shows the molecular basis of the different substrate specificity distinguishing these two classes of nucleoside hydrolases. An "aromatic stacking network" in the active site of the IAG-NH, absent from the IU-NH, imposes the purine specificity. Asp10 is the proposed general base in the reaction mechanism, abstracting a proton from a nucleophilic water molecule. Asp40 (replaced by Asn39 in the IU-NH) is positioned appropriately to act as a general acid and to protonate the purine leaving group. The second general acid, needed for full enzymatic activity, is probably part of a flexible loop located in the vicinity of the active site.