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

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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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.

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Correspondence to David W Christianson.

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The authors declare no competing financial interests.

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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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