Molecular dynamics simulations of the p21ras-p120GAP-GTP complex suggest that the local structure around the catalytic region can be different from that revealed by the x-ray crystal structure. We find that the carbonyl oxygen on the backbone of the arginine finger supplied in trans by p120GAP (Arg789) interacts with a water molecule in the active site that is forming a bridge between the NH2 group of the Gln61 and the g-phosphate of GTP. Thus Arg789 may play a dual role in generating the nucleophile as well as stabilizing the transition state for P-O bond cleavage.
Revised: May 29, 2002 |
Published: May 22, 2001
Citation
Resat H., T. Straatsma, D.A. Dixon, and J.H. Miller. 2001.The Arginine Finger of RasGAP Helps Gln-61 Align the Nucleophilic Water in GAP-Stimulated Hydrolysis of GTP.Proceedings of the National Academy of Sciences of the United States of America 98, no. 11:6033-6038.PNNL-SA-33758.