Structure and inhibition of tuberculosinol synthase and decaprenyl diphosphate synthase from Mycobacterium tuberculosis.
Structure and inhibition of tuberculosinol synthase and decaprenyl diphosphate synthase from Mycobacterium tuberculosis.
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结核菌合酶的结构和抑制作用和二磷酸二磷酸合酶从结核分枝杆菌。
DOI：
10.1021/ja413127v
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发表时间：
2014-02-19
影响因子：
15
通讯作者：
Guo RT
中科院分区：
文献类型：
--
作者：
Chan HC;Feng X;Ko TP;Huang CH;Hu Y;Zheng Y;Bogue S;Nakano C;Hoshino T;Zhang L;Lv P;Liu W;Crick DC;Liang PH;Wang AH;Oldfield E;Guo RT
我们从结核分枝杆菌中获得了细菌二萜合酶、结核菌素/异结核菌素合酶 (Rv3378c) 的结构，这是阻止毒力因子形成的抗感染疗法的靶点。该磷酸酶采用与 Z-或顺式异戊二烯基转移酶相同的折叠。我们还获得了含有结核菌素二磷酸底物以及一种双膦酸盐抑制剂结合结构的结构。这些结构与定点诱变的结果一起表明涉及两个酪氨酸残基的不寻常的作用机制。鉴于 Rv3378c 和结核分枝杆菌顺式十异戊二烯基二磷酸合酶（DPPS；Rv2361c）之间局部和整体结构的相似性，部分基于本文报道的结构，存在开发不仅针对毒力而且针对细胞壁生物合成的抑制剂的可能性。
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.
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影响因子：
3.4
作者：
Lin, Fu-Yang;Zhang, Yonghui;Hensler, Mary;Liu, Yi-Liang;Chow, Ohn A.;Zhu, Wei;Wang, Ke;Pang, Ran;Thienphrapa, Wdee;Nizet, Victor;Oldfield, Eric
通讯作者：
Oldfield, Eric
影响因子：
15
作者：
Mann FM;Xu M;Chen X;Fulton DB;Russell DG;Peters RJ
通讯作者：
Peters RJ
影响因子：
7.3
作者：
Friesner, Richard A.;Murphy, Robert B.;Mainz, Daniel T.
通讯作者：
Mainz, Daniel T.
影响因子：
3.2
作者：
Hoshino, Tsutomu;Nakano, Chiaki;Hara, Takashi
通讯作者：
Hara, Takashi
影响因子：
1.6
作者：
Nakano, Chiaki;Ootsuka, Takahiro;Hoshino, Tsutomu
通讯作者：
Hoshino, Tsutomu