Structure and Inhibition of Tuberculosinol Synthase and Decaprenyl Diphosphate Synthase from Mycobacterium tuberculosis
Chan, Hsiu-Chien1; Feng, Xinxin2; Ko, Tzu-Ping3; Huang, Chun-Hsiang1; Hu, Yumei1; Zheng, Yingying1; Bogue, Shannon2; Nakano, Chiaki4; Hoshino, Tsutomu4; Zhang, Lilan1
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2014-02-19
卷号136期号:7页码:2892-2896
英文摘要We have obtained the structure of the bacterial diterpene synthase, tuberculosinol/iso-tuberculosinol synthase (Rv3378c) from Mycobacterium tuberculosis, a target for anti-infective therapies that block virulence factor formation. This phosphatase adopts the same fold as found in the Z- or cis-prenyltransferases. We also obtained structures containing the tuberculosinyl diphosphate substrate together with one bisphosphonate inhibitor-bound structure. These structures together with the results of site-directed mutagenesis suggest an unusual mechanism of action involving two Tyr residues. Given the similarity in local and global structure between Rv3378c and the M. tuberculosis cis-decaprenyl diphosphate synthase (DPPS; Rv2361c), the possibility exists for the development of inhibitors that target not only virulence but also cell wall biosynthesis, based in part on the structures reported here.
WOS标题词Science & Technology ; Physical Sciences
类目[WOS]Chemistry, Multidisciplinary
研究领域[WOS]Chemistry
关键词[WOS]DITERPENE CYCLASE ; EDAXADIENE ; VIRULENCE
收录类别SCI
语种英语
WOS记录号WOS:000331779800030
公开日期2014-12-23
内容类型期刊论文
源URL[http://124.16.173.210/handle/311007/545]  
专题天津工业生物技术研究所_结构生物学与蛋白酶学实验室 郭瑞庭_期刊论文
作者单位1.Tianjin Inst Ind Biotechnol, Ind Enzymes Natl Engn Lab, Tianjin 300308, Peoples R China
2.Univ Illinois, Dept Chem, Urbana, IL 61801 USA
3.Acad Sinica, Inst Biol Chem, Taipei 11529, Taiwan
4.Niigata Univ, Dept Appl Biol Chem, Niigata 9502181, Japan
5.Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA
推荐引用方式
GB/T 7714
Chan, Hsiu-Chien,Feng, Xinxin,Ko, Tzu-Ping,et al. Structure and Inhibition of Tuberculosinol Synthase and Decaprenyl Diphosphate Synthase from Mycobacterium tuberculosis[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2014,136(7):2892-2896.
APA Chan, Hsiu-Chien.,Feng, Xinxin.,Ko, Tzu-Ping.,Huang, Chun-Hsiang.,Hu, Yumei.,...&Guo, Rey-Ting.(2014).Structure and Inhibition of Tuberculosinol Synthase and Decaprenyl Diphosphate Synthase from Mycobacterium tuberculosis.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,136(7),2892-2896.
MLA Chan, Hsiu-Chien,et al."Structure and Inhibition of Tuberculosinol Synthase and Decaprenyl Diphosphate Synthase from Mycobacterium tuberculosis".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 136.7(2014):2892-2896.
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