Phillips2003 - The Mechanism of Ras GTPase Activation by Neurofibromin

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.

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