Exploring NAG-thiazoline and its derivatives as inhibitors of chitinolytic beta-acetylglucosaminidases
文献类型：期刊论文
| 作者 | Liu, Tian1; Xia, Meng; Zhang, Haitao2; Zhou, Hao3; Wang, Jing1; Shen, Xu2 ; Yang, Qing1
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| 刊名 | FEBS LETTERS
 |
| 出版日期 | 2015-01-02 |
| 卷号 | 589期号:1页码:110-116 |
| 关键词 | beta-Acetylglucosaminidase Chitinolytic enzyme Inhibitor NGT |
| ISSN号 | 1873-3468 |
| DOI | 10.1016/j.febslet.2014.11.032 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| WOS关键词 | ACETYL-D-HEXOSAMINIDASE ; N-ACETYLHEXOSAMINIDASE INHIBITORS ; UNSYMMETRICAL DYADS ; CRYSTAL-STRUCTURES ; D-GLUCOSAMINIDASE ; SANDHOFF-DISEASE ; 8 STEREOISOMERS ; FORCE-FIELD ; TAY-SACHS ; MECHANISM |
| 资助项目 | National High Technology Research and Development Program of China[2011AA10A204] ; National Natural Science Foundation of China[31101671] ; Program for Liaoning Excellent Talents in University[LJQ2014006] ; Fundamental Research Funds for the Central Universities[DUT14LK13] ; NKT R&D Program of China[2012BAK25B03] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000346577700016 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276678]  |
| 专题 | 药理学第三研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Yang, Qing |
| 作者单位 | 1.Dalian Univ Technol, Sch Life Sci & Biotechnol, Dalian 116024, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200237, Peoples R China; 3.Dalian Univ Technol, Key Lab Ind Ecol & Environm Engn, Sch Food & Environm Sci & Technol, Panjin 124000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Tian,Xia, Meng,Zhang, Haitao,et al. Exploring NAG-thiazoline and its derivatives as inhibitors of chitinolytic beta-acetylglucosaminidases[J]. FEBS LETTERS,2015,589(1):110-116. |
| APA | Liu, Tian.,Xia, Meng.,Zhang, Haitao.,Zhou, Hao.,Wang, Jing.,...&Yang, Qing.(2015).Exploring NAG-thiazoline and its derivatives as inhibitors of chitinolytic beta-acetylglucosaminidases.FEBS LETTERS,589(1),110-116. |
| MLA | Liu, Tian,et al."Exploring NAG-thiazoline and its derivatives as inhibitors of chitinolytic beta-acetylglucosaminidases".FEBS LETTERS 589.1(2015):110-116. |
入库方式： OAI收割
来源：上海药物研究所
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