“Head-to-Middle” and “Head-to-Tail” cis-Prenyl Transferases: Structure of Isosesquilavandulyl Diphosphate Synthase

Jian Gao, Tzu Ping Ko, Lu Chen, Satish R. Malwal, Jianan Zhang, Xiangying Hu, Fiona Qu, Weidong Liu, Jian Wen Huang, Ya Shan Cheng, Chun Chi Chen, Yunyun Yang, Yonghui Zhang, Eric Oldfield, Rey Ting Guo

Research output: Contribution to journalArticle

Abstract

We report the first X-ray crystallographic structure of the “head-to-middle” prenyltransferase, isosesquilavandulyl diphosphate synthase, involved in biosynthesis of the merochlorin class of antibiotics. The protein adopts the ζ or cis-prenyl transferase fold but remarkably, unlike tuberculosinol adenosine synthase and other cis-prenyl transferases (e.g. cis-farnesyl, decaprenyl, undecaprenyl diphosphate synthases), the large, hydrophobic side chain does not occupy a central hydrophobic tunnel. Instead, it occupies a surface pocket oriented at 90° to the hydrophobic tunnel. Product chain-length control is achieved by squeezing out the ligand from the conventional allylic S1 binding site, with proton abstraction being achieved using a diphosphate-Asn-Ser relay. The structures revise and unify our thinking as to the mechanism of action of many other prenyl transferases and may also be of use in engineering new merochlorin-class antibiotics.

Original languageEnglish (US)
Pages (from-to)683-687
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number3
DOIs
StatePublished - Jan 15 2018

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Keywords

  • X-ray diffraction
  • antibiotics
  • enzymes
  • isoprenoids
  • protein structures

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Gao, J., Ko, T. P., Chen, L., Malwal, S. R., Zhang, J., Hu, X., Qu, F., Liu, W., Huang, J. W., Cheng, Y. S., Chen, C. C., Yang, Y., Zhang, Y., Oldfield, E., & Guo, R. T. (2018). “Head-to-Middle” and “Head-to-Tail” cis-Prenyl Transferases: Structure of Isosesquilavandulyl Diphosphate Synthase. Angewandte Chemie - International Edition, 57(3), 683-687. https://doi.org/10.1002/anie.201710185