GTP ANALOG HYDROLYSIS BY THE GS PROTEIN - IMPLICATION FOR THE ROLE OFCATALYTIC GLUTAMINE IN THE GTPASE REACTION

Hydrolysis of GTP, bound to members of the G-protein superfamily, term inates their downstream signaling activity, ii conserved glutamine ser ves a critical role in this pivotal guanosine triphosphatase (GTPase) reaction, However, the role of the catalytic glutamine in GTP hydrolys is is still not well understood. We have employed substrate-assisted c atalysis to probe the catalytic mechanism of G(s)alpha using GTP analo gues. These GTP analogues, each having different functional groups, me re designed to support or refute particular putative GTPase mechanisms . We have found that a hydrogen donor group, in close proximity to the gamma-phosphate of GTP, is necessary and sufficient to substitute for the function of the catalytic glutamine in the GTPase reaction. (C) 1 998 Federation of European Biochemical Societies.