title: Ab initio study of the role of lysine 16 for the molecular switching mechanism of Ras protein p21.
abstract: Quantum chemical computations using the ab initio molecular orbital (MO) method have been performed to investigate the molecular switching mechanism of Ras protein p21, which has an important role in intracellular signal cascades. Lys(16) was demonstrated to be crucial to the function of Ras p21, and the hydrolysis of GTP to GDP was found to be an one-step reaction. The potential energy barrier of this hydrolysis reaction from GTP to (GDP + P) was calculated to be approximately 42 kcal/mol. The role of GAP (GTPase-activating protein) was also discussed in terms of the delivery of the water molecules required for the hydrolysis.
authors.affiliation: Laboratory of Physical Chemistry, Faculty of Pharmaceutical Sciences, Chiba University, Chiba-shi 263-8522, Japan. foota@atlas.riken.go.jp
authors.forename: N
authors.initials: N
authors.lastname: Futatsugi
authors.forename: M
authors.initials: M
authors.lastname: Hata
authors.forename: T
authors.initials: T
authors.lastname: Hoshino
authors.forename: M
authors.initials: M
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D016283:Proto-Oncogene Proteins p21(ras); D008239:Lysine