| Autor: |
Chan HC; Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology , Tianjin 300308, China., 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 |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2014 Feb 19; Vol. 136 (7), pp. 2892-6. Date of Electronic Publication: 2014 Feb 05. |
| DOI: |
10.1021/ja413127v |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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