Suppr超能文献

分子动力学模拟揭示了双孢蘑菇吡喃糖脱氢酶在 C2 和 C3 位对 D-葡萄糖氧化的作用机制。

Molecular dynamics simulations give insight into D-glucose dioxidation at C2 and C3 by Agaricus meleagris pyranose dehydrogenase.

机构信息

Food Biotechnology Laboratory, Department of Food Science and Technology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190, Vienna, Austria.

出版信息

J Comput Aided Mol Des. 2013 Apr;27(4):295-304. doi: 10.1007/s10822-013-9645-7. Epub 2013 Apr 17.

Abstract

The flavin-dependent sugar oxidoreductase pyranose dehydrogenase (PDH) from the plant litter-degrading fungus Agaricus meleagris oxidizes D-glucose (GLC) efficiently at positions C2 and C3. The closely related pyranose 2-oxidase (P2O) from Trametes multicolor oxidizes GLC only at position C2. Consequently, the electron output per molecule GLC is twofold for PDH compared to P2O making it a promising catalyst for bioelectrochemistry or for introducing novel carbonyl functionalities into sugars. The aim of this study was to rationalize the mechanism of GLC dioxidation employing molecular dynamics simulations of GLC-PDH interactions. Shape complementarity through nonpolar van der Waals interactions was identified as the main driving force for GLC binding. Together with a very diverse hydrogen-bonding pattern, this has the potential to explain the experimentally observed promiscuity of PDH towards different sugars. Based on geometrical analysis, we propose a similar reaction mechanism as in P2O involving a general base proton abstraction, stabilization of the transition state, an alkoxide intermediate, through interaction with a protonated catalytic histidine followed by a hydride transfer to the flavin N5 atom. Our data suggest that the presence of the two potential catalytic bases His-512 and His-556 increases the versatility of the enzyme, by employing the most suitably oriented base depending on the substrate and its orientation in the active site. Our findings corroborate and rationalize the experimentally observed dioxidation of GLC by PDH and its promiscuity towards different sugars.

摘要

依赖黄素的糖氧化还原酶吡喃糖脱氢酶(PDH)来自植物凋落物降解真菌蘑菇,能有效地在 C2 和 C3 位置氧化 D-葡萄糖(GLC)。与之密切相关的木聚糖 2-氧化酶(P2O)来自 Trametes multicolor 仅在 C2 位置氧化 GLC。因此,与 P2O 相比,每个 GLC 分子的电子输出是两倍,这使其成为生物电化学或向糖中引入新型羰基官能团的有前途的催化剂。本研究的目的是通过 GLC-PDH 相互作用的分子动力学模拟来合理化 GLC 双氧化的机制。通过非极性范德华相互作用的形状互补被确定为 GLC 结合的主要驱动力。与非常多样化的氢键模式相结合,这有可能解释 PDH 对不同糖的实验观察到的混杂性。基于几何分析,我们提出了与 P2O 类似的反应机制,涉及一般碱质子的提取、通过与质子化的催化组氨酸相互作用稳定过渡态、通过形成烷氧基中间体,随后氢化物转移到黄素 N5 原子。我们的数据表明,两个潜在催化碱 His-512 和 His-556 的存在通过根据底物及其在活性位点中的取向采用最合适的定向碱,增加了酶的多功能性。我们的发现证实并合理化了 PDH 对 GLC 的双氧化及其对不同糖的混杂性的实验观察。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/070c/3657087/750d5c5431ea/10822_2013_9645_Fig1_HTML.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