Structure and Inhibition of Tuberculosinol Synthase and Decaprenyl Diphosphate Synthase from Mycobacterium tuberculosis | Zendy

HsiuChien Chan | Zendy; Xinxin Feng | Zendy; TzuPing Ko | Zendy; Chun-Hsiang Huang | Zendy; Yumei Hu | Zendy; Yingying Zheng | Zendy; Shan Bogue | Zendy; Chiaki Nakano | Zendy; Tsutomu Hoshino | Zendy; Lilan Zhang | Zendy; Pin Lv | Zendy; Wenting Liu | Zendy; Dean C. Crick | Zendy; PoHuang Liang | Zendy; Andrew H.J. Wang | Zendy; Eric Oldfield | Zendy; ReyTing Guo | Zendy

Open Access

Structure and Inhibition of Tuberculosinol Synthase and Decaprenyl Diphosphate Synthase from Mycobacterium tuberculosis

Author(s) -

HsiuChien Chan,

Xinxin Feng,

TzuPing Ko,

Chun-Hsiang Huang,

Yumei Hu,

Yingying Zheng,

Shan Bogue,

Chiaki Nakano,

Tsutomu Hoshino,

Lilan Zhang,

Pin Lv,

Wenting Liu,

Dean C. Crick,

PoHuang Liang,

Andrew H.J. Wang,

Eric Oldfield,

ReyTing Guo

Publication year - 2014

Publication title -

journal of the american chemical society

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 7.115

H-Index - 612

eISSN - 1520-5126

pISSN - 0002-7863

DOI - 10.1021/ja413127v

Subject(s) - chemistry , atp synthase , mycobacterium tuberculosis , biochemistry , virulence , stereochemistry , polyketide synthase , enzyme , biosynthesis , virulence factor , mutagenesis , tuberculosis , mutation , gene , polyketide , medicine , pathology

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research