Diterpene cyclases and the nature of the isoprene fold

Rong Cao, Yonghui Zhang, Francis M. Mann, Cancan Huang, Dushyant Mukkamala, Michael P. Hudock, Matthew E. Mead, Sladjana Prisic, Ke Wang, Fu Yang Lin, Ting Kai Chang, Reuben J. Peters, Eric Oldfield

Research output: Contribution to journalArticlepeer-review

Abstract

The structures and mechanism of action of many terpene cyclases are known, but no structures of diterpene cyclases have yet been reported. Here, we propose structural models based on bioinformatics, site-directed mutagenesis, domain swapping, enzyme inhibition, and spectroscopy that help explain the nature of diterpene cyclase structure, function, and evolution. Bacterial diterpene cyclases contain ∼20 α-helices and the same conserved "QW" and DxDD motifs as in triterpene cyclases, indicating the presence of a βγ barrel structure. Plant diterpene cyclases have a similar catalytic motif and βγ-domain structure together with a third, α-domain, forming an αβγ structure, and in H +-initiated cyclases, there is an EDxxD-like Mg2+/ diphosphate binding motif located in the γ-domain. The results support a new view of terpene cyclase structure and function and suggest evolution from ancient (βγ) bacterial triterpene cyclases to (βγ) bacterial and thence to (αβγ) plant diterpene cyclases.

Original languageEnglish (US)
Pages (from-to)2417-2432
Number of pages16
JournalProteins: Structure, Function and Bioinformatics
Volume78
Issue number11
DOIs
StatePublished - Aug 15 2010

Keywords

  • Cyclase
  • Diterpene
  • Farnesyl diphosphate
  • Homology model
  • Isoprenoid
  • Triterpene

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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