Normal mode analysis and comparative study of intrinsic dynamics of alcohol oxidase enzymes from GMC protein family

Glucose-Methanol-Choline (GMC) family enzymes are very important in catalyzing the oxidation of a wide range of structurally diverse substrates. Enzymes that constitute the GMC family, share a common tertiary fold but < 25% sequence identity. Cofactor FAD, FAD binding signature motif, and similar structural scaffold of the active site are common features of oxidoreductase enzymes of the GMC family. Protein functionality mainly depends on protein three-dimensional structures and dynamics. In this study, we used the normal mode analysis method to search the intrinsic dynamics of GMC family enzymes. We have explored the dynamical behavior of enzymes with unique substrate catabolism and active site characteristics from different classes of the GMC family. Analysis of individual enzymes and comparative ensemble analysis of enzymes from different classes has shown conserved dynamic motion at FAD binding sites. The present study revealed that GMC enzymes share a strong dynamic similarity (Bhattacharyya coefficient >90% and root mean squared inner product >52%) despite low sequence identity across the GMC family enzymes. The study predicts that local deformation energy between atoms of the enzyme may be responsible for the catalysis of different substrates. This study may help that intrinsic dynamics can be used to make meaningful classifications of proteins or enzymes from different organisms. Communicated by Ramaswamy H. Sarma

葡萄糖-甲醇-胆碱（Glucose-Methanol-Choline, GMC）家族酶在催化结构多样的多种底物的氧化反应中发挥关键作用。构成GMC家族的各类酶虽序列一致性低于25%，但拥有共同的三级折叠结构。黄素腺嘌呤二核苷酸（Flavin Adenine Dinucleotide, FAD）作为辅因子、FAD结合特征基序，以及活性位点的相似结构支架，均为GMC家族氧化还原酶的共有特征。蛋白质的功能主要由其三维结构与动力学特性决定。本研究采用正则模式分析方法，探究GMC家族酶的内在动力学行为。我们针对GMC家族不同分支中，具备独特底物分解代谢特性与活性位点特征的酶类，系统分析了其动力学行为。对单种酶的单独分析以及不同分支酶的整体比较分析结果均显示，GMC家族酶的FAD结合位点存在保守的动态运动模式。本研究表明，尽管GMC家族酶的序列一致性较低，但它们之间存在极强的动态相似性（巴塔查里亚系数＞90%，均方内积＞52%）。本研究推测，酶原子间的局部形变能或许是其催化不同底物的核心机制。本研究可为利用内在动力学特性对不同来源的蛋白质或酶类开展合理分类提供理论支撑。由Ramaswamy H. Sarma转交