Suppr超能文献

L-半乳糖脱氢酶的结构特征:维生素 C 生物合成的必需酶。

Structural Characterization of L-Galactose Dehydrogenase: An Essential Enzyme for Vitamin C Biosynthesis.

机构信息

São Carlos Institute of Physics, University of São Paulo, Avenida João Dagnone 1100, São Carlos, SP 13563-120, Brazil.

Laboratory of Biochemistry, Instituto Butantan, Av. Vital Brasil, São Paulo 1500, Brazil.

出版信息

Plant Cell Physiol. 2022 Aug 17;63(8):1140-1155. doi: 10.1093/pcp/pcac090.

Abstract

In plants, it is well-known that ascorbic acid (vitamin C) can be synthesized via multiple metabolic pathways but there is still much to be learned concerning their integration and control mechanisms. Furthermore, the structural biology of the component enzymes has been poorly exploited. Here we describe the first crystal structure for an L-galactose dehydrogenase [Spinacia oleracea GDH (SoGDH) from spinach], from the D-mannose/L-galactose (Smirnoff-Wheeler) pathway which converts L-galactose into L-galactono-1,4-lactone. The kinetic parameters for the enzyme are similar to those from its homolog from camu camu, a super-accumulator of vitamin C found in the Peruvian Amazon. Both enzymes are monomers in solution and have a pH optimum of 7, and their activity is largely unaffected by high concentrations of ascorbic acid, suggesting the absence of a feedback mechanism acting via GDH. Previous reports may have been influenced by changes of the pH of the reaction medium as a function of ascorbic acid concentration. The structure of SoGDH is dominated by a (β/α)8 barrel closely related to aldehyde-keto reductases (AKRs). The structure bound to NAD+ shows that the lack of Arg279 justifies its preference for NAD+ over NADP+, as employed by many AKRs. This favors the oxidation reaction that ultimately leads to ascorbic acid accumulation. When compared with other AKRs, residue substitutions at the C-terminal end of the barrel (Tyr185, Tyr61, Ser59 and Asp128) can be identified to be likely determinants of substrate specificity. The present work contributes toward a more comprehensive understanding of structure-function relationships in the enzymes involved in vitamin C synthesis.

摘要

在植物中,众所周知抗坏血酸(维生素 C)可以通过多种代谢途径合成,但关于它们的整合和控制机制仍有许多需要了解。此外,该成分酶的结构生物学研究还很不完善。在这里,我们描述了第一个晶体结构 L-半乳糖脱氢酶[Spinacia oleracea GDH(菠菜 SoGDH)],它来自 D-甘露糖/L-半乳糖(Smirnoff-Wheeler)途径,可将 L-半乳糖转化为 L-半乳糖酸-1,4-内酯。该酶的动力学参数与来自其同源物的参数相似,其同源物来自于 Camu Camu,Camu Camu 是亚马逊地区秘鲁的一种维生素 C 的超积累植物。两种酶在溶液中均为单体,最适 pH 值为 7,其活性受高浓度抗坏血酸的影响很小,这表明不存在通过 GDH 起作用的反馈机制。先前的报告可能受到反应介质 pH 值随抗坏血酸浓度变化的影响。SoGDH 的结构主要由(β/α)8 桶组成,与醛酮还原酶(AKRs)密切相关。与 NAD+结合的结构表明,Arg279 的缺失解释了其对 NAD+的偏好,而许多 AKRs 则使用 NADP+。这有利于氧化反应,最终导致抗坏血酸的积累。与其他 AKRs 相比,可以确定桶的 C 末端的残基取代(Tyr185、Tyr61、Ser59 和 Asp128)是底物特异性的可能决定因素。本工作有助于更全面地了解维生素 C 合成中涉及的酶的结构-功能关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0749/9381564/7e0ac5a0ba59/pcac090f1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验