Structure and Inhibition of Tuberculosinol Synthase and Decaprenyl Diphosphate Synthase from Mycobacterium tuberculosis
作者： Hsiu-Chien Chan , Xinxin Feng , Tzu-Ping Ko , Chun-Hsiang Huang , Yumei Hu
DOI: 10.1021/JA413127V
关键词:
摘要: We have obtained the structure of 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 same fold as found in Z- or cis-prenyltransferases. also structures containing tuberculosinyl diphosphate substrate together with one bisphosphonate inhibitor-bound structure. These results site-directed mutagenesis suggest an unusual mechanism action involving two Tyr residues. Given similarity local and global between Rv3378c M. tuberculosis cis-decaprenyl (DPPS; Rv2361c), possibility exists development inhibitors not only but cell wall biosynthesis, based part on reported here.
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