|School or College
|College of Pharmacy; College of Science; School of Medicine
|Biochemistry; Medicinal Chemistry; Chemistry
|Poulter, Charles Dale
|Laskovics, F. Mark; Krafick, James M.
|Prenyltransferase. Kinetic studies of the 1'-4 coupling reaction with avian liver enzyme.
|Prenyltransferase catalyzes the sequential, irreversible 1'-4 condensation of isopentenyl-PP with dimethylallyl-PP and geranyl-PP to yield farnesyl-PP. A kinetic study shows substrate inhibition by isopentenyl-PP at concentrations above 0.7 microM when the concentration of geranyl-PP is 1.0 microM or less as a result of binding by the homoallylic substrate to the allylic region of the active site. Inhibition studies were carried out with the products, farnesyl-PP and PPi, and dead-end inhibitors 2-F-isopentenyl-PP and 2-F-geranyl-PP, analogues for the normal substrates. Competitive patterns were seen for farnesyl-PP and 2-F-geranyl-PP when geranyl-PP was varied, while noncompetitive patterns were found for all other combinations. A minor form of PPi, MgHPPi-, is implicated as the species of PPi in the magnesium-containing buffer which binds most tightly to the enzyme. This observation explains why K's for PPi calculated from the total concentration of PPi are much larger than K's for the organic pyrophosphates. The lack of regiospecificity in the binding of isopentenyl-PP, as evidenced by substrate inhibition patterns, introduces an element of ambiguity into mechanistic interpretations, and it is not possible to distinguish between ordered and random mechanisms on the basis of inhibition studies.
|American Society for Biochemistry and Molecular Biology (ASBMB)
|Birds; Kinetics; Structure-Activity Relationship; Substrate Specificity
|Dimethylallyltranstransferase; Liver; Transferases
|J Biol Chem. 1979 Oct 10;254(19):9458-63. Laskovics FM, Krafcik JM, Poulter CD. Prenyltransferase. Kinetic studies of the 1'-4 coupling reaction with avian liver enzyme. Retrieved April 16, 2007 from http://www.jbc.org/cgi/reprint/254/19/9458.
|Copyright © 1978 American Society for Biochemistry and Molecular Biology. All rights reserved.