Schweins, T. and Geyer, M. and Scheffzek, K. and Warshel, A. and Kalbitzer, Hans Robert and Wittinghofer, A. (1995) Substrate-assisted catalysis as a mechanism for GTP hydrolysis of p21ras and other GTP-binding proteins. Nature structural biology 2 (1), pp. 36-44.
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Despite many advances in understanding the structure and function of GTP-binding proteins the mechanism by which these molecules switch from the GTP-bound on-state to the GDP-bound off-state is still poorly understood. Theoretical studies suggest that the activation of the nucleophilic water which hydrolyzes GTP needs a general base. Such a base could not be located in any of the many GTP-binding proteins. Here we present a unique type of linear free energy relationships that not only supports a mechanism for p21ras in which the substrate GTP itself acts as the catalytic base driving the GTPase reaction but can also help to explain why certain mutants of p21ras are oncogenic and others are not.
|Institutions:||Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer|
|Subjects:||500 Science > 570 Life sciences|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||08 Sep 2010 08:08|
|Last Modified:||08 Sep 2010 08:08|