Electrostatic control of GTP and GDP binding in the oncoprotein p21ras

摘要: Abstract Background: p21 ras is one of the GTP-binding proteins that act as intercellular molecular switches. The GTP-bound form sends a growth-promoting signal terminated once protein cycled back into its GDP-bound form. interaction guanine-nucleotide-exchange factors (GEFs) with leads to activation by promoting GDP→GTP exchange. Oncogenic mutations trap in biological active Other interfere activity GEF. Thus, it important explore structural basis for action different mutations. Results crystal structures are correlated binding affinities GTP and GDP calculating relevant electrostatic energies. It demonstrated such calculations can provide road map location ‘hot' residues whose likely change functional properties protein. Furthermore, effect specific on consistent those observed. This helps analyze locate functionally parts Conclusion Our indicate main chain provides major contribution energies nucleotides probably plays key role relaying GEF action. Analysis proper function GEFs suggests region comprising 62—67 GEF-binding site. analysis our computer simulations propagated P-loop (residues 10–17) through between Gly60 Gly12. then reduces main-chain dipoles nucleotide. Finally, results also suggest possible relationship GTP→GDP transition catalytic GTPase-activating