In silico modelling of the function of disease-related CAZymes.

IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Alba Nin-Hill, Beatriz Piniello, Carme Rovira
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引用次数: 2

Abstract

In silico modelling of proteins comprises a diversity of computational tools aimed to obtain structural, electronic, and/or dynamic information about these biomolecules, capturing mechanistic details that are challenging to experimental approaches, such as elusive enzyme-substrate complexes, short-lived intermediates, and reaction transition states (TS). The present article gives the reader insight on the use of in silico modelling techniques to understand complex catalytic reaction mechanisms of carbohydrate-active enzymes (CAZymes), along with the underlying theory and concepts that are important in this field. We start by introducing the significance of carbohydrates in nature and the enzymes that process them, CAZymes, highlighting the conformational flexibility of their carbohydrate substrates. Three commonly used in silico methods (classical molecular dynamics (MD), hybrid quantum mechanics/molecular mechanics (QM/MM), and enhanced sampling techniques) are described for nonexpert readers. Finally, we provide three examples of the application of these methods to unravel the catalytic mechanisms of three disease-related CAZymes: β-galactocerebrosidase (GALC), responsible for Krabbe disease; α-mannoside β-1,6-N-acetylglucosaminyltransferase V (MGAT5), involved in cancer; and O-fucosyltransferase 1 (POFUT1), involved in several human diseases such as leukemia and the Dowling-Degos disease.

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疾病相关CAZymes功能的计算机模拟。
蛋白质的计算机建模包括多种计算工具,旨在获得有关这些生物分子的结构,电子和/或动态信息,捕获对实验方法具有挑战性的机制细节,例如难以捉摸的酶-底物复合物,短寿命中间体和反应过渡态(TS)。本文为读者提供了关于使用硅建模技术来理解碳水化合物活性酶(CAZymes)的复杂催化反应机制的见解,以及在该领域重要的基础理论和概念。我们首先介绍碳水化合物在自然界中的重要性和处理它们的酶,CAZymes,强调它们的碳水化合物底物的构象灵活性。三种常用的硅方法(经典分子动力学(MD),混合量子力学/分子力学(QM/MM)和增强采样技术)描述了非专业读者。最后,我们提供了三个应用这些方法的例子来揭示三种疾病相关的酶的催化机制:β-半乳糖脑苷酶(GALC),负责克拉伯病;α-甘露糖苷β-1,6- n -乙酰氨基葡萄糖转移酶V (MGAT5)参与癌症;O- focusyltransferase 1 (POFUT1),参与多种人类疾病,如白血病和Dowling-Degos病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Essays in biochemistry
Essays in biochemistry 生物-生化与分子生物学
CiteScore
10.50
自引率
0.00%
发文量
105
审稿时长
>12 weeks
期刊介绍: Essays in Biochemistry publishes short, digestible reviews from experts highlighting recent key topics in biochemistry and the molecular biosciences. Written to be accessible for those not yet immersed in the subject, each article is an up-to-date, self-contained summary of the topic. Bridging the gap between the latest research and established textbooks, Essays in Biochemistry will tell you what you need to know to begin exploring the field, as each article includes the top take-home messages as summary points. Each issue of the journal is guest edited by a key opinion leader in the area, and whether you are continuing your studies or moving into a new research area, the Journal gives a complete picture in one place. Essays in Biochemistry is proud to publish Understanding Biochemistry, an essential online resource for post-16 students, teachers and undergraduates. Providing up-to-date overviews of key concepts in biochemistry and the molecular biosciences, the Understanding Biochemistry issues of Essays in Biochemistry are published annually in October.
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