QM/MM Study on Enzymatic Mechanism in Sinigrin Biosynthesis  

黑芥子苷生物合成中酶催化机理的QM/MM研究

作　　者：Ya-Jie Guo Ya-Jun Liu 郭雅洁;刘亚军(北京师范大学化学学院,理论与计算光化学教育部重点实验室,北京100875;北京师范大学珠海校区,自然科学高等研究院先进材料研究中心,珠海519087)

机构地区：[1]Key Laboratory of Theoretical and Computational Photochemistry,Ministry of Education,College of Chemistry,Beijing Normal University,Beijing 100875,China [2]Center for Advanced Materials Research,Advanced Institute of Natural Sciences,Beijing Normal University at Zhuhai,Zhuhai 519087,China

出　　处：《Chinese Journal of Chemical Physics》2022年第1期193-199,I0041-I0057,I0064,共25页化学物理学报（英文）

基　　金：supported by the National Natural Science Foundation of China(No.21973005)。

摘　　要：As the major and abundant type of glucosinolates(GL)in plants,sinigrin has potential functions in promoting health and insect defense.The final step in the biosynthesis of sinigrin core structure is highly representative in GL compounds,which corresponds to the process from 3-methylthiopropyl ds-GL to 3-methylthiopropyl GL catalyzed by sulfotransferase(SOT).However,due to the lack of the crystallographic structure of SOT complexed with the 3-methylthiopropyl GL,little is known about this sulfonation process.Fortunately,the crystal structure of SOT 18 from Arabidopsis thaliana(At SOT18)containing the substance(sinigrin)similar to 3-methylthiopropyl GL has been determined.To understand the enzymatic mechanism,we employed molecular dynamics(MD)simulation and quantum mechanics combined with molecular mechanics(QM/MM)methods to study the conversion from ds-sinigrin to sinigrin catalyzed by AtSOT18.The calculated results demonstrate that the reaction occurs through a concerted dissociative mechanism.Moreover,Lys93,Thr96,Thr97,Tyr130,His155,and two enzyme peptide chains(Pro92-Lys93 and Gln95-Thr96-Thr97)play a role in positioning the substrates and promoting the catalytic reaction by stabilizing the transition state geometry.Particularly,His155 acts as a catalytic base while Lys93 acts as a catalytic acid in the reaction process.The presently proposed concerted dissociative mechanism explains the role of At SOT18 in sinigrin biosynthesis,and could be instructive for the study of GL biosynthesis catalyzed by other SOTs.

关 键 词：SINIGRIN SULFOTRANSFERASE Molecular dynamics Quantum mechanics and molecular mechanics 

分 类 号：TQ426.97[化学工程]