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首页> 外文期刊>Journal of Molecular Biology >Characterization of two novel aldo-keto reductases from Arabidopsis: expression patterns, broad substrate specificity, and an open active-site structure suggest a role in toxicant metabolism following stress.
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Characterization of two novel aldo-keto reductases from Arabidopsis: expression patterns, broad substrate specificity, and an open active-site structure suggest a role in toxicant metabolism following stress.

机译：拟南芥中两种新的醛基酮还原酶的表征：表达模式，广泛的底物特异性和开放的活性位点结构表明应激后毒物代谢中的作用。

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Aldo-keto reductases (AKRs) are widely distributed in nature and play numerous roles in the metabolism of steroids, sugars, and other carbonyls. They have also frequently been implicated in the metabolism of exogenous and endogenous toxicants, including those stimulated by stress. Although the Arabidopsis genome includes at least 21 genes with the AKR signature, very little is known of their functions. In this study, we have screened the Arabidopsis thaliana genomic sequence for genes with significant homology to members of the mammalian AKR1 family and identified four homologues for further study. Following alignment of the predicted protein sequences with representatives from the AKR superfamily, the proteins were ascribed not to the AKR1 family but to the AKR4C subfamily, with the individual designations of AKR4C8, AKR4C9, AKR4C10, and AKR4C11. Expression of two of the genes, AKR4C8 and AKR4C9, has been shown to be coordinately regulated and markedly induced by various forms of stress. The genes have been overexpressed in bacteria, and recombinant proteins have been purified and crystallized. Both enzymes display NADPH-dependent reduction of carbonyl compounds, typical of the superfamily, but will accept a very wide range of substrates, reducing a range of steroids, sugars, and aliphatic and aromatic aldehydes/ketones, although there are distinct differences between the two enzymes. We have obtained high-resolution crystal structures of AKR4C8 (1.4 A) and AKR4C9 (1.25 A) in ternary complexes with NADP(+) and acetate. Three extended loops, present in all AKRs and responsible for defining the cofactor- and substrate-binding sites, are shorter in the 4C subfamily compared to other AKRs. Consequently, the crystal structures reveal open and accommodative substrate-binding sites, which correlates with their broad substrate specificity. It is suggested that the primary role of these enzymes may be to detoxify a range of toxic aldehydes and ketones produced during stress, although the precise nature of the principal natural substrates remains to be determined.
机译：醛基酮还原酶（AKR）在自然界中广泛分布，并在类固醇，糖和其他羰基化合物的代谢中发挥许多作用。它们还经常与外源性和内源性毒物的代谢有关，包括受压力刺激的那些。尽管拟南芥基因组至少包含21个带有AKR签名的基因，但对其功能的了解却很少。在这项研究中，我们筛选了拟南芥基因组序列中与哺乳动物AKR1家族成员具有显着同源性的基因，并鉴定了四个同源物以供进一步研究。在将预测的蛋白质序列与AKR超家族的代表进行比对后，这些蛋白质不是归属于AKR1家族而是归属于AKR4C亚家族，并分别命名为AKR4C8，AKR4C9，AKR4C10和AKR4C11。两种形式的基因AKR4C8和AKR4C9的表达已被多种形式的应激协调调节并明显诱导。基因已在细菌中过表达，重组蛋白已纯化和结晶。两种酶均显示出NADPH依赖性的羰基化合物还原，这是超家族的典型特征，但会接受非常广泛的底物，从而降低了一系列的类固醇，糖以及脂族和芳族醛/酮，尽管两者之间存在明显差异酶。我们已经获得了与NADP（+）和乙酸酯三元配合物的AKR4C8（1.4 A）和AKR4C9（1.25 A）的高分辨率晶体结构。与其他AKR相比，在4C亚家族中，所有AKR中均存在三个负责定义辅因子和底物结合位点的延伸环。因此，晶体结构揭示了开放的和可调节的底物结合位点，这与它们广泛的底物特异性相关。建议这些酶的主要作用可能是对应激过程中产生的一系列有毒的醛和酮进行解毒，尽管主要天然底物的确切性质尚待确定。

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