首页> 外文期刊>Journal of Molecular Biology >Structural Basis for the Aldolase and Epimerase Activities of Staphylococcus aureus Dihydroneopterin Aldolase.
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Structural Basis for the Aldolase and Epimerase Activities of Staphylococcus aureus Dihydroneopterin Aldolase.

机译:金黄色葡萄球菌双氢蝶呤醛缩酶的醛缩酶和差向异构酶活性的结构基础。

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摘要

Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) and the epimerization of DHNP to 7,8-dihydromonopterin (DHMP). Although crystal structures of the enzyme from several microorganisms have been reported, no structural information is available about the critical interactions between DHNA and the trihydroxypropyl moiety of the substrate, which undergoes bond cleavage and formation. Here, we present the structures of Staphylococcus aureus DHNA (SaDHNA) in complex with neopterin (NP, an analog of DHNP) and with monapterin (MP, an analog of DHMP), filling the gap in the structural analysis of the enzyme. In combination with previously reported SaDHNA structures in its ligand-free form (PDB entry 1DHN) and in complex with HP (PDB entry 2DHN), four snapshots for the catalytic center assembly along the reaction pathway can be derived, advancing our knowledge about the molecular mechanism of SaDHNA-catalyzed reactions. An additionalstep appears to be necessary for the epimerization of DHMP to DHNP. Three active site residues (E22, K100, and Y54) function coordinately during catalysis: together, they organize the catalytic center assembly, and individually, each plays a central role at different stages of the catalytic cycle.
机译:二氢蝶呤醛缩酶(DHNA)催化7,8-二氢蝶呤(DHNP)转化为6-羟甲基-7,8-二氢蝶呤(HP)和DHNP的差向异构化为7,8-二氢蝶呤(DHMP)。尽管已报道了几种微生物的酶的晶体结构,但尚无关于DHNA与底物的三羟丙基部分之间进行键断裂和形成的关键相互作用的结构信息。在这里,我们介绍了金黄色葡萄球菌DHNA(SaDHNA)与新in呤(NP,DHNP的类似物)和莫纳菌素(MP,DHMP的类似物)的复合结构,填补了酶结构分析的空白。与先前报道的无配体形式的SaDHNA结构(PDB条目1DHN)以及与HP复杂的SaDHNA结构(PDB条目2DHN)相结合,可以得出沿着反应路径的催化中心组装的四个快照,这进一步提高了我们对分子的认识SaDHNA催化反应的机理。对于DHMP向DHNP进行差向异构化,似乎需要采取其他步骤。在催化过程中,三个活性位点残基(E22,K100和Y54)协同起作用:它们共同构成了催化中心组件,并且各自独立地在催化循环的不同阶段发挥着核心作用。

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