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Isoprenoid Biosynthesis: Ferraoxetane or Allyl Anion Mechanism for IspH Catalysis?

Authors

  • Jikun Li,

    1. Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, 607 South Mathews Avenue, Urbana, IL 61801 (USA)
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    • These authors contributed equally to this work.

  • Dr. Ke Wang,

    1. Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801 (USA)
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    • These authors contributed equally to this work.

  • Prof. Dr. Tatyana I. Smirnova,

    1. Department of Chemistry, North Carolina State University, Raleigh, NC 27695 (USA)
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  • Rahul L. Khade,

    1. Department of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Castle Point on Hudson, Hoboken NJ 07030 (USA)
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  • Prof. Dr. Yong Zhang,

    1. Department of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Castle Point on Hudson, Hoboken NJ 07030 (USA)
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  • Prof. Dr. Eric Oldfield

    Corresponding author
    1. Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801 (USA)
    • Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801 (USA)

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  • This work was supported by NIH grant (GM065307) to E.O., NIH grant (GM085774) to Y.Z., NSF grant MCB-0843632 to T.I.S. and equipment grants from NIH (S10RR023614), NSF (CHE-0840501), and the North Carolina Biotechnology Center (NCBC 2009-IDG-1015). J.L. was supported by a pre-doctoral fellowship from the American Heart Association, Midwest Affiliate (11PRE7500042). We thank Drs. Hassan Jomaa and Jochen Wiesner for providing the A. aeolicus IspH expression system and Mark J. Nilges for assistance with the EPR spectroscopy.

Abstract

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The catalytic mechanism of the enzyme IspH, involved in formation of isopentenyl diphosphate and dimethylallyl diphosphate, was investigated by using HYSCORE spectroscopy combined with DFT. The results indicate the formation of an allyl anion bound to a HiPIP-like oxidized 4Fe–4S cluster, rather than formation of a cyclic, ferraoxetane intermediate, as has been proposed elsewhere.

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