Yeast protein farnesyltransferase: a pre-steady-state kinetic analysis

Biochemistry
J R Mathis, C D Poulter

Abstract

Protein farnesyltransferase catalyzes alkylation of the cysteine in a carboxy-terminal CaaX motif where a is typically an aliphatic amino acid and X is alanine, methionine, serine, glutamine, or cysteine by a farnesyl residue. The modification enhances the lipophilicity of farnesylated proteins and promotes their association with membranes as part of their normal cellular function. Among the proteins modified by farnesyl residues is Ras, an important component in the signal transduction network for cell division that has been implicated in several forms of human cancer. In this paper, we describe isotope trapping, rapid quench, and single turnover experiments with the yeast enzyme using farnesyl diphosphate and the short peptide RTRCVIA as substrates. The kinetic constants for substrate binding, chemistry, and product release were determined from a fit of the differential equations describing the minimal catalytic mechanism to the kinetic data by numerical integration. Rate constants for chemistry and product release were 10.5 and 3.5 s(-1), respectively. The dissociation rate constant (33 s(-1)) for release of peptide from the ternary enzyme-substrate complex was three times larger than the rate constant for chemistry. The ent...Continue Reading

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Citations

Dec 22, 2004·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sérgio Filipe SousaMaria João Ramos
Feb 10, 2009·Biochemistry·James L HouglandCarol A Fierke
Oct 11, 2002·Nature·Stephen B LongLorena S Beese
Nov 30, 2006·Chembiochem : a European Journal of Chemical Biology·Benjamin P DuckworthMark D Distefano
Mar 22, 2016·Biochemistry·Daniel J GrundyRudolf K Allemann
Jan 9, 2007·Molecular and Biochemical Parasitology·Richard T EastmanWesley C Van Voorhis
Jul 28, 1999·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·P K Jeffery
Jul 8, 1997·Biochemistry·J R MathisJ Chappell

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