Biomaterial Database

The interaction of Ras with GTPase-activating proteins. 1997

A Wittinghofer, and K Scheffzek, and M R Ahmadian

Max-Planck-Institut für molekulare Physiologie, Dortmund, Germany. alfred.wittinghofer@mpi-dortmund.mpg.de

Ras plays a major role as a molecular switch in many signal transduction pathways which lead to cell growth and differentiation. The GTPase reaction of Ras is of central importance in the function of the switch since it terminates Ras-effector interactions. GTPase-activating proteins (GAPs) accelerate the very slow intrinsic hydrolysis reaction of the GTP-bound Ras by several orders of magnitude and thereby act as presumably negative regulators of Ras action. The GTP hydrolysis of oncogenic mutants of Ras remains unaltered. In this review we discuss recent biochemical and structural findings relating to the mechanism of GAP action, which strengthen the hypothesis that GAP accelerates the actual cleavage step by stabilizing the transition state of the phosphoryl transfer reaction.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D018631	ras Proteins	Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein ONCOGENE PROTEIN P21(RAS) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.	Gene Products, ras,ras GTPase,ras Protein,ras GTPases,GTPase, ras,GTPases, ras,Protein, ras,ras Gene Products
D020690	GTPase-Activating Proteins	Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.	GAP Proteins,GAP Protein,GTPase-Activating Protein,GTPase Activating Protein,GTPase Activating Proteins
D020703	ras GTPase-Activating Proteins	PROTEINS that specifically activate the GTP-phosphohydrolase activity of RAS PROTEINS.	ras-GAPs,ras-GAP,GTPase-Activating Proteins, ras,ras GAP,ras GAPs,ras GTPase Activating Proteins