周豪

个人信息Personal Information

副教授

博士生导师

硕士生导师

主要任职:化工海洋与生命学院副院长

性别:男

毕业院校:大连理工大学

学位:博士

所在单位:化工海洋与生命学院

学科:环境工程

办公地点:海洋科学与技术学院 D05 307

联系方式:zhouhao@dlut.edu.cn

电子邮箱:zhouhao@dlut.edu.cn

扫描关注

论文成果

当前位置: 中文主页 >> 科学研究 >> 论文成果

Exploring NAG-thiazoline and its derivatives as inhibitors of chitinolytic beta-acetylglucosaminidases

点击次数:

论文类型:期刊论文

发表时间:2015-01-02

发表刊物:FEBS LETTERS

收录刊物:SCIE、PubMed

卷号:589

期号:1

页面范围:110-116

ISSN号:0014-5793

关键字:beta-Acetylglucosaminidase; Chitinolytic enzyme; Inhibitor; NGT

摘要:NAG-thiazoline (NGT) and its derivatives are well-known inhibitors against most beta-acetylglucosaminidases (beta-GlcNAcases) except for insect and bacterial chitinolytic beta-GlcNAcases, including the molting-indispensable OfHex1 from the insect Ostrinia furnacalis. Here, we report the co-crystal structure of OfHex1 in complex with NGT. This structure reveals a large active pocket in OfHex1 that may account for the poor inhibitory activity of NGT. To test this hypothesis, a bulky substituent was designed and synthesized on the thiazoline ring of NGT. The resulting compound (NMAGT) was determined to be a submicromolar inhibitor of OfHex1 with a K-i value of 0.13 mu M, which is 600-fold lower than K-i value of NGT. Molecular dynamics simulation analysis supported the good fit of NMAGT to the active pocket. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.