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Diterpene cyclases and the nature of the isoprene fold

Authors

  • Rong Cao,

    1. Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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    • Rong Cao, Yonghui Zhang, and Francis M. Mann contributed equally to this work.

  • Yonghui Zhang,

    1. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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    • Rong Cao, Yonghui Zhang, and Francis M. Mann contributed equally to this work.

  • Francis M. Mann,

    1. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011
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    • Rong Cao, Yonghui Zhang, and Francis M. Mann contributed equally to this work.

  • Cancan Huang,

    1. Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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  • Dushyant Mukkamala,

    1. Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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  • Michael P. Hudock,

    1. Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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  • Matthew E. Mead,

    1. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011
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  • Sladjana Prisic,

    1. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011
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  • Ke Wang,

    1. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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  • Fu-Yang Lin,

    1. Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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  • Ting-Kai Chang,

    1. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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  • Reuben J. Peters,

    Corresponding author
    1. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011
    • Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011
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  • Eric Oldfield

    Corresponding author
    1. Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
    2. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801
    • Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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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. Proteins 2010. © 2010 Wiley-Liss, Inc.

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