Dataset Information

Phillips2003 - The Mechanism of Ras GTPase Activation by Neurofibromin

ABSTRACT: Phillips2003 - The Mechanism of Ras GTPase Activation by Neurofibromin A mathematical model for Ras-GTP activation by neurofibromin and the kinetic rates of the relevant reactions. This model is described in the article: The mechanism of Ras GTPase activation by neurofibromin. Phillips RA, Hunter JL, Eccleston JF, Webb MR. Biochemistry 2003 Apr; 42(13): 3956-3965 Abstract: Individual rate constants have been determined for each step of the Ras.GTP hydrolysis mechanism, activated by neurofibromin. Fluorescence intensity and anisotropy stopped-flow measurements used the fluorescent GTP analogue, mantGTP (2'(3')-O-(N-methylanthraniloyl)GTP), to determine rate constants for binding and release of neurofibromin. Quenched flow measurements provided the kinetics of the hydrolytic cleavage step. The fluorescent phosphate sensor, MDCC-PBP was used to measure phosphate release kinetics. Phosphate-water oxygen exchange, using (18)O-substituted GTP and inorganic phosphate (P(i)), was used to determine the extent of reversal of the hydrolysis step and of P(i) binding. The data show that neurofibromin and P(i) dissociate from the NF1.Ras.GDP.P(i) complex with identical kinetics, which are 3-fold slower than the preceding cleavage step. A model is presented in which the P(i) release is associated with the change of Ras from "GTP" to "GDP" conformation. In this model, the conformation change on P(i) release causes the large change in affinity of neurofibromin, which then dissociates rapidly. This model is hosted on BioModels Database and identified by: BIOMD0000000692. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Sharat Vayttaden

PROVIDER: BIOMD0000000692 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000692?filename=BIOMD0000000692-biopax2.owl	Owl
	BIOMD0000000692?filename=BIOMD0000000692-biopax3.owl	Owl
	BIOMD0000000692?filename=BIOMD0000000692-matlab.m	Other
	BIOMD0000000692?filename=BIOMD0000000692-octave.m	Other
	BIOMD0000000692?filename=BIOMD0000000692.m	Other

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The mechanism of Ras GTPase activation by neurofibromin.

Phillips Robert A RA Hunter Jackie L JL Eccleston John F JF Webb Martin R MR

Biochemistry 20030401 13

Individual rate constants have been determined for each step of the Ras.GTP hydrolysis mechanism, activated by neurofibromin. Fluorescence intensity and anisotropy stopped-flow measurements used the fluorescent GTP analogue, mantGTP (2'(3')-O-(N-methylanthraniloyl)GTP), to determine rate constants for binding and release of neurofibromin. Quenched flow measurements provided the kinetics of the hydrolytic cleavage step. The fluorescent phosphate sensor, MDCC-PBP was used to measure phosphate rele ...[more]

PMID: 12667087

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