PMID: 7013805Mar 31, 1981Paper

Prenyltransferase; determination of the binding mechanism and individual kinetic constants for farnesylpyrophosphate synthetase by rapid quench and isotope partitioning experiments

Biochemistry
F M Laskovics, C D Poulter

Abstract

The 1'-4 condensation reaction catalyzed by farnesylpyrophosphate synthetase was examined by using rapid quench and isotope partitioning experiments. E.Mg2+-isopentyl-PP (PP = pyrophosphate) is not catalytically competent, as evidenced by failure to trap the complex with Mg2+-geranyl-PP at concentrations as high as 3.2 mM. In contrast, the concentration of Mg2+-isopentenyl-PP required for one-half maximal trapping (K 1/2) of E.Mg2+-geranyl-PP is 1.4 muM. The results strongly support an ordered mechanism for the 1'-4 condensation reaction, with addition of the allylic substrate before Mg2+-isopentenyl-PP. At short reaction times, a burst phase corresponding to accumulation of Mg2+-farnesyl-PP on the surface of the enzyme, followed by a slower, steady-state release of products, is observed. Evaluation of individual kinetic constants for the reaction indicates that the rates for addition of Mg2+-geranyl-PP to the enzyme (k1 = 4.9 X 10(6) M-1 s-1) and addition of Mg2+-isopentenyl-PP to E.Mg2+-geranyl-PP (k3 = 2 X 10(6) m-1 s-1) are below the diffusion-controlled limit. The rate-limiting step at steady state is isomerization of E.Mg2+-farnesyl-PP-Mg2+-PPi or release of products (k6 = 0.1 s-1). During the course of isotope partitioni...Continue Reading

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Citations

Apr 1, 1994·Protein Science : a Publication of the Protein Society·A ChenC D Poulter
Mar 31, 2005·Archives of Biochemistry and Biophysics·Sarah PicaudPeter E Brodelius
Jul 12, 2002·Insect Biochemistry and Molecular Biology·Stephanie E Sen, Andrea E Sperry
Dec 9, 2000·Biochimica Et Biophysica Acta·K C Wang, S Ohnuma
Dec 7, 2006·Journal of the American Chemical Society·Hirekodathakallu V Thulasiram, C Dale Poulter
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·L Song, C D Poulter
Dec 22, 1999·Biochemical and Biophysical Research Communications·R K Keller, S J Fliesler
Dec 24, 1996·Proceedings of the National Academy of Sciences of the United States of America·L C TarshisC D Poulter
Jan 16, 2013·European Journal of Medicinal Chemistry·Marion RecherJuan B Rodriguez
Aug 3, 2013·Chemical Reviews·Philip D KiserKrzysztof Palczewski
Feb 6, 2008·Current Opinion in Chemical Biology·David W Christianson
Jul 9, 2011·Protein Science : a Publication of the Protein Society·Juan E DiazGregory A Weiss
Jul 1, 1992·Archives of Biochemistry and Biophysics·J C Gebler, C D Poulter
Dec 5, 2013·Bioorganic & Medicinal Chemistry·Mariana Ferrer-CasalJuan B Rodriguez
Mar 7, 2014·Acta Crystallographica. Section D, Biological Crystallography·Srinivas AripiralaSandra B Gabelli
May 24, 2014·The Journal of Biological Chemistry·Hsin-Yang ChangAndrew H J Wang
Sep 27, 2020·Bioorganic & Medicinal Chemistry Letters·Walid M AbdelmagidMartin E Tanner

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