4KT8

The complex structure of Rv3378c-Y51FY90F with substrate, TPP

4KT8 の概要

• エントリーDOI: 10.2210/pdb4kt8/pdb
• 関連するPDBエントリー: 3VX5 3VX9 3VXA 3W3I
• 分子名称: Diterpene synthase, PHOSPHATE ION, (2E)-3-methyl-5-[(1R,2S,8aS)-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalen-1-yl]pent-2-en-1-yl trihydrogen diphosphate, ... (4 entities in total)
• 機能のキーワード: diterpene synthase, hydrolase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34774.84

構造登録者

Chan, H.C.,Feng, X.,Ko, T.P.,Huang, C.H.,Hu, Y.,Zheng, Y.,Bogue, S.,Nakano, C.,Hoshino, T.,Zhang, L.,Lv, P.,Liu, W.,Crick, D.C.,Liang, P.H.,Wang, A.H.,Oldfield, E.,Guo, R.T. (登録日: 2013-05-20, 公開日: 2014-02-26, 最終更新日: 2023-11-08)

主引用文献

Chan, H.C.,Feng, X.,Ko, T.P.,Huang, C.H.,Hu, Y.,Zheng, Y.,Bogue, S.,Nakano, C.,Hoshino, T.,Zhang, L.,Lv, P.,Liu, W.,Crick, D.C.,Liang, P.H.,Wang, A.H.,Oldfield, E.,Guo, R.T.
Structure and inhibition of tuberculosinol synthase and decaprenyl diphosphate synthase from Mycobacterium tuberculosis.
J.Am.Chem.Soc., 136:2892-2896, 2014

PubMed Abstract: 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.

PubMed: 24475925
DOI: 10.1021/ja413127v

実験手法

X-RAY DIFFRACTION (2.4 Å)