5UHV

wild-type NRas bound to GppNHp

Summary for 5UHV

• Entry DOI: 10.2210/pdb5uhv/pdb
• Descriptor: GTPase NRas, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: nras, gtpase, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 19435.82

Authors

Reid, D.,Johnson, C.,Salter, S.,Mattos, C. (deposition date: 2017-01-12, release date: 2017-06-28, Last modification date: 2023-10-04)

Primary citation

Johnson, C.W.,Reid, D.,Parker, J.A.,Salter, S.,Knihtila, R.,Kuzmic, P.,Mattos, C.
The small GTPases K-Ras, N-Ras, and H-Ras have distinct biochemical properties determined by allosteric effects.
J. Biol. Chem., 292:12981-12993, 2017

PubMed Abstract: H-Ras, K-Ras, and N-Ras are small GTPases that are important in the control of cell proliferation, differentiation, and survival, and their mutants occur frequently in human cancers. The G-domain, which catalyzes GTP hydrolysis and mediates downstream signaling, is 95% conserved between the Ras isoforms. Because of their very high sequence identity, biochemical studies done on H-Ras have been considered representative of all three Ras proteins. We show here that this is not a valid assumption. Using enzyme kinetic assays under identical conditions, we observed clear differences between the three isoforms in intrinsic catalysis of GTP by Ras in the absence and presence of the Ras-binding domain (RBD) of the c-Raf kinase protein (Raf-RBD). Given their identical active sites, isoform G-domain differences must be allosteric in origin, due to remote isoform-specific residues that affect conformational states. We present the crystal structure of N-Ras bound to a GTP analogue and interpret the kinetic data in terms of structural features specific for H-, K-, and N-Ras.

PubMed: 28630043
DOI: 10.1074/jbc.M117.778886

Experimental method

X-RAY DIFFRACTION (1.672 Å)