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Enzyme-Dependent [4+2] Cycloaddition Depends on Lid-like Interaction of the N-Terminal Sequence with the Catalytic Core in PyrI4

文献类型：期刊论文

作者Zheng, Qingfei2; Guo, Yujiao2; Yang, Linlin1; Zhao, Zhixiong2; Wu, Zhuhua2; Zhang, Hua2; Liu, Jianping2; Cheng, Xiaofang2; Wu, Jiequn2,3; Yang, Huaiyu1
刊名CELL CHEMICAL BIOLOGY
出版日期2016-03-17
卷号23期号:3页码:352-360
ISSN号2451-9448
DOI10.1016/j.chembiol.2016.01.005
文献子类Article
英文摘要The Diels-Alder [4 + 2] cycloaddition reaction is one of the most powerful and elegant organic synthesis methods for forming 6-membered molecules and has been known for nearly a century. However, whether and how enzymes catalyze this type of reaction is still not completely clear. Here we focus on PyrI4, an enzyme found in the biosynthetic pathway of pyrroindomycins where it catalyzes the formation of a spiro-conjugate via an enzyme-dependent exo-selective [4 + 2] cycloaddition reaction. We report the crystal structures of PyrI4 alone and in complex with its product. Comparative analysis of these structures, combined with biochemical analysis, lead us to propose a unique trapping mechanism whereby the lid-like action of the N-terminal tail imposes conformational constraints on the b barrel catalytic core, which enhances the proximity and polarization effects of reactive groups (1,3-diene and alkene) to drive cyclization in a regio- and stereospecific manner. This work represents an important step toward the wider application of enzyme-catalyzed [4 + 2] cyclization for synthetic purposes.
WOS关键词DIELS-ALDER REACTION ; BIOSYNTHESIS ; PYRROINDOMYCINS ; POLYKETIDES ; CYCLIZATION ; LL-42D005 ; INSIGHTS ; MODEL ; NMR
资助项目MST[2013CB836900] ; Thousand Talents Program, STCSM of China[15JC1400400] ; Thousand Talents Program, SRSSA of China[13QA1404300] ; NSFC of China[91313000] ; NSFC of China[31430005] ; NSFC of China[21520102004] ; NSFC of China[31300064] ; STCSM of China[15JC1400400] ; STCSM of China[14JC1407700] ; MST of China[2012AA02A706]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000381508300008
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/276099]  
专题药物发现与设计中心
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Pan, Lifeng; Liu, Wen
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China;
3.Huzhou Ctr Biosynthet Innovat, 1366 Hongfeng Rd, Huzhou 313000, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Qingfei,Guo, Yujiao,Yang, Linlin,et al. Enzyme-Dependent [4+2] Cycloaddition Depends on Lid-like Interaction of the N-Terminal Sequence with the Catalytic Core in PyrI4[J]. CELL CHEMICAL BIOLOGY,2016,23(3):352-360.
APA Zheng, Qingfei.,Guo, Yujiao.,Yang, Linlin.,Zhao, Zhixiong.,Wu, Zhuhua.,...&Liu, Wen.(2016).Enzyme-Dependent [4+2] Cycloaddition Depends on Lid-like Interaction of the N-Terminal Sequence with the Catalytic Core in PyrI4.CELL CHEMICAL BIOLOGY,23(3),352-360.
MLA Zheng, Qingfei,et al."Enzyme-Dependent [4+2] Cycloaddition Depends on Lid-like Interaction of the N-Terminal Sequence with the Catalytic Core in PyrI4".CELL CHEMICAL BIOLOGY 23.3(2016):352-360.

入库方式： OAI收割

来源：上海药物研究所

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