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首页> 外文期刊>Biochemistry >Structure of a Sedoheptulose 7?Phosphate Cyclase: ValA from Streptomyces hygroscopicus
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Structure of a Sedoheptulose 7?Phosphate Cyclase: ValA from Streptomyces hygroscopicus

机译：七肽7？磷酸环化酶的结构：吸水链霉菌的ValA。

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Sedoheptulose 7-phosphate cyclases (SH7PCs) encompass three enzymes involved in producing the core cyclitol structures of pseudoglycosides and similar bioactive natural products. One such enzyme is ValA from Streptomyces hygroscopicus subsp. jinggangensis 5008, which makes 2-epi-5- epi-valiolone as part of the biosynthesis of the agricultural antifungal agent validamycin A. We present, as the first SH7PC structure, the 2.1 ? resolution crystal structure of ValA in complex with NAD~+ and Zn~(2+) cofactors. ValA has a fold and active site organization resembling those of the sugar phosphate cyclase dehydroquinate synthase (DHQS) and contains two notable, previously unrecognized interactions between NAD~+ and Asp side chains conserved in all sugar phosphate cyclases that may influence catalysis. Because the domains of ValA adopt a nearly closed conformation even though no sugar substrate is present, comparisons with a ligand-bound DHQS provide a model for aspects of substrate binding. One striking active site difference is a loop that adopts a distinct conformation as a result of an Asp → Asn change with respect to DHQS and alters the identity and orientation of a key Arg residue. This and other active site differences in ValA are mostly localized to areas where the ValA substrate differs from that of DHQS. Sequence comparisons with a second SH7PC making a product with distinct stereochemistry lead us to postulate that the product stereochemistry of a given SH7PC is not the result of events taking place during catalysis but is accomplished by selective binding of either the α or β pyranose anomer of the substrate.
机译：七肽七磷酸环化酶（SH7PCs）包含三种与产生假糖苷和类似生物活性天然产物的核心环醇结构有关的酶。一种这样的酶是来自吸水链霉菌亚种的ValA。作为农业抗真菌剂有效霉素A生物合成的一部分，生产2-表位-5-表-缬氨酸的jinggangensis5008。作为第一个SH7PC结构，我们提出了2.1？ NAD〜+和Zn〜（2+）辅因子复合物中ValA的高分辨晶体结构。 ValA具有类似于糖磷酸环化酶脱氢奎宁酸合酶（DHQS）的折叠和活性位点组织，并且在所有可能影响催化作用的所有糖磷酸化环化酶中保守了NAD〜+和Asp侧链之间的两个显着的，以前无法识别的相互作用。因为即使不存在糖底物，ValA的结构域也采用几乎封闭的构象，所以与配体结合的DHQS的比较为底物结合的各个方面提供了一个模型。一个显着的活性位点差异是一个环，该环由于DHQS的Asp→Asn变化而采用不同的构象，并改变了关键Arg残基的身份和方向。 ValA的这种和其他活性位点差异主要定位在ValA底物与DHQS底物不同的区域。与第二个SH7PC的序列比较可制得具有独特立体化学的产物，这使我们推测给定SH7PC的产物立体化学不是催化过程中发生的事件的结果，而是通过选择性结合该化合物的α或β吡喃糖异构体来实现的。基质。

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