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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structure and activity of Yersinia pestis 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as a novel target for the development of antiplague therapeutics.
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Structure and activity of Yersinia pestis 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as a novel target for the development of antiplague therapeutics.

机译：鼠疫杆菌的结构和活动6-hydroxymethyl-7,8-dihydropterinpyrophosphokinase作为小说的目标antiplague疗法的发展。

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摘要

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate-biosynthetic pathway and is essential for microorganisms but absent from mammals. HPPK catalyzes Mg(2+)-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). Previously, three-dimensional structures of Escherichia coli HPPK (EcHPPK) have been determined at almost every stage of its catalytic cycle and the reaction mechanism has been established. Here, the crystal structure of Yersinia pestis HPPK (YpHPPK) in complex with HP and an ATP analog is presented together with thermodynamic and kinetic characterizations. The two HPPK molecules differ significantly in a helix-loop area (alpha2-Lp3). YpHPPK has lower affinities than EcHPPK for both nucleotides and HP, but its rate constants for the mechanistic steps of both chemical transformation and product release are comparable with those of EcHPPK. Y. pestis, which causes plague, is a category A select agent according to the Centers for Disease Control and Prevention (CDC). Therefore, these structural and biochemical data are valuable for the design of novel medical countermeasures against plague.
机译：6-Hydroxymethyl-7,8-dihydropterinpyrophosphokinase (HPPK)是一个关键酶folate-biosynthetic通路,是至关重要的微生物但缺席哺乳动物。催化镁(2 +)端依赖pyrophosphoryl从ATP转移到6-hydroxymethyl-7,8-dihydropterin(赫顿).以前,三维结构大肠杆菌HPPK (EcHPPK)决定在几乎每一个阶段的催化周期和反应机理建立。鼠疫杆菌HPPK (YpHPPK)在复杂与惠普和一个ATP模拟提出了一起热力学和动力学特征。两个HPPK分子在一个方面有显著的差异helix-loop区域(alpha2-Lp3)。比EcHPPK核苷酸和亲和力惠普,但其机械的速率常数步骤的化学转换和产品释放与EcHPPK具有可比性。导致鼠疫耶尔,一个类别选择代理根据疾控制和预防中心(CDC)。结构和生化数据是有价值的小说医疗的设计对策对鼠疫。

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