title: Computational study of a transition state analog of phosphoryl transfer in the Ras-RasGAP complex: AlF(x) versus MgF3-.
abstract: The structures of the complexes between Ras*GDP bound to RasGAP in the presence of three probable gamma-phosphate analogs (AlF3, AlF4- and MgF3-) for the transition state (TS) of the hydrolysis of guanosine triphosphate (GTP) by the Ras-RasGAP enzymes have been modeled by quantum mechanical-molecular mechanical (QM/MM) calculations. These simulations contribute to the dispute on the nature of the TS in the hydrolysis reaction, since medium resolution X-ray crystallography cannot discern among stereochemically similar isoelectronic species (e.g., AlF3 or MgF3-). The optimized geometry for each structure has been found starting from experimental coordinates of one of them (PDBID: 1WQ1). Direct comparison of the experimental and computed geometry configurations in the immediate vicinity of the active site suggests that MgF3- is the most likely candidate for the phosphate analog in the experimental structure.
authors.affiliation: Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, 119992, Russian Federation.
authors.forename: Bella L
authors.initials: BL
authors.lastname: Grigorenko
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Nemukhin
authors.forename: Raul E
authors.initials: RE
authors.lastname: Cachau
authors.forename: Igor A
authors.initials: IA
authors.lastname: Topol
authors.forename: Stanley K
authors.initials: SK
authors.lastname: Burt
mesh_terms: D001665:Binding Sites; D003201:Computers; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D010710:Phosphates / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D020703:ras GTPase-Activating Proteins / Q000737:chemistry* / Q000378:metabolism*; D018631:ras Proteins / Q000737:chemistry* / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D010710:Phosphates; D020703:ras GTPase-Activating Proteins; C085379:rho GTPase-activating protein; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein