The hydrolysis of GTP in ras p21 triggers conformational changes that regulate the signal transduction pathway. An important active sight residue is Gln61, which has been found to be mutated in 30% of human tumors. The dynamics of the active site conformation is studied using molecular dynamics simulation of two independent structures of the GTP-bound uncomplexed enzyme. Two distinct conformations of the enzyme are observed, in which the side chain residue Gln61 is in different orientations. Essential dynamics analysis is used to describe the essential motions in the transition between the two conformations. results are compared with earlier simulations of ras p21 and its complex with GTP-ase activating protein p21-GAP.
Revised: January 3, 2002 |
Published: December 1, 2001
Citation
Silva T.A., J.H. Miller, and T. Straatsma. 2001.Revisiting the Structural Flexibility of the Complex p21ras-GTP: The Catalytic Conformation of the Molecular Switch II.Proteins. Structure, Function, and Genetics 45, no. 4:297-312.PNNL-SA-34522.