WHY HAVE MUTAGENESIS STUDIES NOT LOCATED THE GENERAL BASE IN RAS P21

Ras p21 plays a major role in the control of cell growth, and oncogeni c mutations of this protein have been found in human cancers. Unfortun ately, the detailed mode of action of pas p21 is still unclear, in spi te of the great interest in this protein and the availability of its X -ray crystal structure. In particular, mutagenesis studies of differen t active site residues could not identify the general base for GIP hyd rolysis. Here we tackle this question using a computer simulation appr oach with clear and reliable energy considerations and conclude that t he most likely general base is the bound CTP itself. Obviously, the id entification of such a general base cannot be easily accomplished by m utagenesis experiments.