Transition state analysis of model and enzymatic prenylation reactions

Stepan Lenevich, Juhua Xu, Ayako Hosokawa, Christopher J. Cramer, Mark D. Distefano

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16 Scopus citations


To obtain a transition state (TS) structure for an enzyme-catalyzed prenylation reaction, SN1 and SN2 model substitution reactions with dimethylallyl chloride were first studied. 13C Kinetic isotope effects (KIEs) for the model reactions were measured by a natural abundance NMR method and used to validate the computational methods that would be used in the subsequent determination of the enzymatic TS structure. Using a primary 13C KIE and a secondary 2H KIE measured via mass spectrometry, a TS structure for the enzyme-catalyzed reaction was computed; a density functional level of electronic structure theory using the mPW1N functional in combination with the 6-31+G(d) basis set was employed for those calculations. That structure has a C-O bond length of 1.69 Å and a C-S bond length of 3.70 Å. While the former bond length is similar to that for a nonenzymatic SN2 reaction, the latter is considerably (0.90 Å) longer, indicating that the enzyme effects catalysis via an "exploded" TS structure.

Original languageEnglish (US)
Pages (from-to)5796-5797
Number of pages2
JournalJournal of the American Chemical Society
Issue number18
StatePublished - May 9 2007


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