NDLI: Fluoride complexes of oncogenic Ras mutants to study the Ras-RasGap interaction.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gremer, Lothar Gilsbach, Bernd Ahmadian, Mohammad Reza Wittinghofer, Alfred
Description	Country affiliation: Germany Author Affiliation: Gremer L ( Abteilung Strukturelle Biologie, Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Strasse 11, D-44227 Dortmund, Germany.)
Abstract	Down-regulation of Ras signalling is mediated by specific GTPase-activating proteins (GAPs), which stimulate the very slow GTPase reaction of Ras by 10(5)-fold. The basic features of the GAP activity involve the stabilisation of both switch regions of Ras in the transition state, and the insertion of an arginine finger. In the case of oncogenic Ras mutations, the features of the active site are disturbed. To understand these features in more detail, we have investigated the effects of oncogenic mutations of Ras and compared the GAP-stimulated GTPase reaction with the ability to form GAP-mediated aluminium or beryllium fluoride complexes. In general we find a correlation between the size of the amino acid at position 12, the GTPase activity and ability to form aluminium fluoride complexes. While Gly12 is very sensitive to even the smallest possible structural change, Gly13 is much less sensitive to steric hindrance, but is sensitive to charge. Oncogenic mutants of Ras defective in the GTPase activity can however form ground-state GppNHp complexes with GAP, which can be mimicked by beryllium fluoride binding. We show that beryllium fluoride complexes are less sensitive to structural changes and report on a state close to but different from the ground state of the GAP-stimulated GTPase reaction.
File Format	HTM / HTML
ISSN	14316730
Issue Number	9
Volume Number	389
e-ISSN	14374315
Journal	Biological Chemistry
Language	English
Publisher	Walter de Gruyter
Publisher Date	2008-09-01
Publisher Place	Germany
Access Restriction	Subscribed
Subject Keyword	Discipline Biochemistry Beryllium Metabolism Fluorides Gtp Phosphohydrolase Activators Gtp Phosphohydrolases Gtpase-activating Proteins Proto-oncogene Proteins P21(ras) Down-regulation Humans Mutant Proteins Mutation Genetics Journal Article
Content Type	Text
Resource Type	Article
Subject	Clinical Biochemistry Biochemistry Molecular Biology

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