Covalent Modification of a Cysteine Residue in the XPB Subunit of the General Transcription Factor TFIIH Through Single Epoxide Cleavage of the Transcription Inhibitor Triptolide

• DOI: 10.1002/anie.201408817
• Publication Date: 2014-12-12T22:25:22Z
• Authors: Qing‐Li He; Denis V. Titov; Jing Li; Minjia Tan; Zhaohui Ye; Yingming Zhao; Daniel Romo; Jun O. Liu
• Keywords: Triptolide; Transcription; Sulforaphane

Abstract Triptolide is a key component of the traditional Chinese medicinal plant Thunder God Vine and has potent anticancer immunosuppressive activities. It an irreversible inhibitor eukaryotic transcription through covalent modification XPB, subunit general factor TFIIH. Cys342 XPB was identified as residue that undergoes by 12,13‐epoxide group triptolide. Mutation to threonine conferred resistance triptolide on mutant protein. Replacement endogenous wild‐type with Cys342Thr in HEK293T cell line rendered it completely resistant triptolide, thus validating physiologically relevant target Together, these results deepen our understanding interaction between have implications for future development new analogues leads drugs.