1WQ1

RAS-RASGAP COMPLEX

Summary for 1WQ1

• Entry DOI: 10.2210/pdb1wq1/pdb
• Descriptor: H-RAS, P120GAP, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: ras, gap, signal transduction, growth regulation, gtp hydrolysis, transition state, complex (gtp-binding-gtpase activation), complex (gtp-binding-gtpase activation) complex, complex (gtp-binding/gtpase activation)
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side: P01112; Cytoplasm: P20936
• Total number of polymer chains: 2
• Total formula weight: 57649.95

Authors

Scheffzek, K.,Ahmadian, M.R.,Kabsch, W.,Wiesmueller, L.,Lautwein, A.,Schmitz, F.,Wittinghofer, A. (deposition date: 1997-07-03, release date: 1998-07-15, Last modification date: 2024-10-30)

Primary citation

Scheffzek, K.,Ahmadian, M.R.,Kabsch, W.,Wiesmuller, L.,Lautwein, A.,Schmitz, F.,Wittinghofer, A.
The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.
Science, 277:333-338, 1997

PubMed Abstract: The three-dimensional structure of the complex between human H-Ras bound to guanosine diphosphate and the guanosine triphosphatase (GTPase)-activating domain of the human GTPase-activating protein p120GAP (GAP-334) in the presence of aluminum fluoride was solved at a resolution of 2.5 angstroms. The structure shows the partly hydrophilic and partly hydrophobic nature of the communication between the two molecules, which explains the sensitivity of the interaction toward both salts and lipids. An arginine side chain (arginine-789) of GAP-334 is supplied into the active site of Ras to neutralize developing charges in the transition state. The switch II region of Ras is stabilized by GAP-334, thus allowing glutamine-61 of Ras, mutation of which activates the oncogenic potential, to participate in catalysis. The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations. Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state.

PubMed: 9219684
DOI: 10.1126/science.277.5324.333

Experimental method

X-RAY DIFFRACTION (2.5 Å)