文献类型：期刊文献

英文题名：Molecular dynamics simulation of iminosugar inhibitor-glycosidase complex:: Insight into the binding mechanism of 1-deoxynojirimycin and isofagomine toward β-glucosidase

作者：Zhou, JM; Zhou, JH; Meng, Y; Chen, MB

机构：[1]Chinese Acad Sci, Shanghai Inst Organ Chem, Dept Comp Chem & Cheminformat, Shanghai 200032, Peoples R China;[2]E China Univ Sci & Technol, Chem & Pharmaceut Inst, Shanghai 200237, Peoples R China

年份：2006

卷号：2

期号：1

起止页码：157

外文期刊名：JOURNAL OF CHEMICAL THEORY AND COMPUTATION

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000235051500019)】；

语种：英文

摘要：The binding mechanism of iminosugar inhibitor 1-deoxynojirimycin and isofagomine toward beta-glucosidase was studied with nanosecond time scale molecular dynamics. Four different systems were analyzed according to the different protonated states of inhibitor and enzyme (acid/base carboxyl group, Glul 66). The simulations gained quite a reasonable result according to the thermodynamic experimental fact. Further conclusions were made including the following: (1) 1-deoxynojirimycin binds with the beta-glucosidase as conjugate acid forms; (2) the slow onset inhibition of isofagomine aims to slow deprotonation of the acid/base carboxyl group which is caused by a nearly zero hydrogen bond interaction between the hydroxyls of the acid/ base carboxyl group; and (3) the nucleophile carboxyl group plays an important role when the inhibitor binds with glucosidase.