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首页> 外文期刊>Journal of Molecular Biology >Structural Insights into the Neuroprotective-acting Carbonyl Reductase Sniffer of Drosophila melanogaster.
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Structural Insights into the Neuroprotective-acting Carbonyl Reductase Sniffer of Drosophila melanogaster.

机译：果蝇的神经保护作用羰基还原酶嗅探器的结构见解。

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摘要

In vivo studies with the fruit-fly Drosophila melanogaster have shown that the Sniffer protein prevents age-dependent and oxidative stress-induced neurodegenerative processes. Sniffer is a NADPH-dependent carbonyl reductase belonging to the enzyme family of short-chain dehydrogenases/reductases (SDRs). The crystal structure of the homodimeric Sniffer protein from Drosophila melanogaster in complex with NADP(+) has been determined by multiple-wavelength anomalous dispersion and refined to a resolution of 1.75A. The observed fold represents a typical dinucleotide-binding domain as detected for other SDRs. With respect to the cofactor-binding site and the region referred to as substrate-binding loop, the Sniffer protein shows a striking similarity to the porcine carbonyl reductase (PTCR). This loop, in both Sniffer and PTCR, is substantially shortened compared to other SDRs. In most enzymes of the SDR family this loop adopts a well-defined conformation only after substrate binding and remains disordered in the absence of any bound ligands or even if only the dinucleotide cofactor is bound. In the structure of the Sniffer protein, however, the conformation of this loop is well defined, although no substrate is present. Molecular modeling studies provide an idea of how binding of substrate molecules to Sniffer could possibly occur.
机译：对果蝇果蝇的体内研究表明，嗅嗅蛋白可防止年龄依赖性和氧化应激诱导的神经变性过程。嗅探器是NADPH依赖性羰基还原酶，属于短链脱氢酶/还原酶（SDR）的酶家族。果蝇的同二聚体嗅探蛋白的晶体结构与NADP（+）的复合物已通过多波长异常色散确定并提纯至1.75A的分辨率。观察到的折叠代表对其他SDR检测到的典型二核苷酸结合结构域。关于辅因子结合位点和称为底物结合环的区域，嗅探蛋白显示出与猪羰基还原酶（PTCR）的惊人相似性。与其他SDR相比，Sniffer和PTCR中的此循环都大大缩短了。在大多数SDR家族的酶中，该环仅在底物结合后才采用明确定义的构象，并且在不存在任何结合配体或什至仅结合二核苷酸辅因子的情况下仍保持无序。然而，在嗅探蛋白的结构中，尽管不存在底物，但该环的构型已得到很好的定义。分子建模研究提供了一个想法，即底物分子如何与嗅探器结合。

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