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Structure and mechanism of the diterpene cyclase ent-copalyl diphosphate synthase

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Abstract

The structure of ent-copalyl diphosphate synthase reveals three α-helical domains (α, β and γ), as also observed in the related diterpene cyclase taxadiene synthase. However, active sites are located at the interface of the βγ domains in ent-copalyl diphosphate synthase but exclusively in the α domain of taxadiene synthase. Modular domain architecture in plant diterpene cyclases enables the evolution of alternative active sites and chemical strategies for catalyzing isoprenoid cyclization reactions.

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Figure 1: ent-Copalyl diphosphate synthase (CPS).
Figure 2: Binding of substrate analog 1 in the active site of CPS.
Figure 3: Initiation of the class II diterpene synthase reaction by general acid catalysis.

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Acknowledgements

We thank the US National Institutes of Health for grants GM56838 (D.W.C.), GM13956 (R.M.C.) and GM76324 (R.J.P.) for support of this research. Additionally, we thank the Advanced Photon Source at Argonne National Laboratory for beamline access.

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Author notes

  1. Huayou Hu

    Present address: Current address: Department of Chemistry, Huaiyin Normal University, Huaian, Jiangsu, China.,

Authors and Affiliations

  1. Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Mustafa Köksal & David W Christianson

  2. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA

    Huayou Hu & Robert M Coates

  3. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa, USA

    Reuben J Peters

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  1. Mustafa Köksal
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  2. Huayou Hu
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  3. Robert M Coates
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  4. Reuben J Peters
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  5. David W Christianson
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Contributions

M.K. and D.W.C. performed the X-ray crystallographic studies. H.H. and R.M.C. synthesized terpenoid diphosphate ligands. R.J.P. supplied the AtCPSd84 construct, and M.K. prepared the final CPS construct that yielded crystals. All authors contributed to the interpretation of the results and preparation of the manuscript.

Corresponding author

Correspondence to David W Christianson.

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The authors declare no competing financial interests.

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Supplementary Methods and Supplementary Results (PDF 3963 kb)

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Köksal, M., Hu, H., Coates, R. et al. Structure and mechanism of the diterpene cyclase ent-copalyl diphosphate synthase. Nat Chem Biol 7, 431–433 (2011). https://doi.org/10.1038/nchembio.578

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