@article {2514,
	title = {Mechanism of Dimethylallyltryptophan Synthase: Evidence for a Dimethylallyl Cation Intermediate in an Aromatic Prenyltransferase Reaction},
	journal = {Journal of the American Chemical Society},
	volume = {131},
	number = {39},
	year = {2009},
	note = {ISI Document Delivery No.: 502DCTimes Cited: 3Cited Reference Count: 31Luk, Louis Y. P. Tanner, Martin E.},
	month = {Oct},
	pages = {13932-13933},
	type = {Article},
	abstract = {Dimethylallyltryptophan synthase is an aromatic prenyltransferase that catalyzes an electrophilic aromatic substitution reaction between dimethylallyl diphosphate (DMAPP) and L-tryptophan. The synthase is found in a variety of fungi, where it catalyzes the first committed step in the biosynthesis of the ergot alkaloids. The enzymatic reaction could follow either a dissociative mechanism involving a discrete dimethylallyl cation intermediate or an associative mechanism in which the indole ring directly displaces diphosphate in a single step. In this work, positional isotope exchange (PIX) experiments are presented in support of a dissociative mechanism. When [1-O-18]-DMAPP is subjected to the synthase reaction and recovered starting material is analyzed, 15\% of the O-18-label is found to have scrambled from a bridging to a nonbridging position on the alpha-phosphorus. Kinetic isotope effect studies show that steps involved in the formation of the arenium ion intermediate are rate-determining, and therefore the scrambling occurs during the lifetime of the dimethylallyl cation/diphosphate ion pair. Similarly, when the unreactive substrate analogue, 6-fluorotryptophan, was employed, complete scrambling of the O-18-label. in DMAPP was observed. To our knowledge, this is the first observation of PIX in any prenyltransferase reaction, and it provides strong evidence supporting the existence of a carbocation intermediate.},
	isbn = {0002-7863},
	doi = {10.1021/ja906485u},
	author = {Luk, L. Y. P. and Tanner, M. E.}
}
