title: Why does mutation of Gln61 in Ras by the nitro analog NGln maintain activity of Ras-GAP in hydrolysis of guanosine triphosphate?
abstract: Interpretation of the experiments showing that the Ras-GAP protein complex maintains activity in guanosine triphosphate (GTP) hydrolysis upon replacement of Glu61 in Ras with its unnatural nitro analog, NGln, is an important issue for understanding details of chemical transformations at the enzyme active site. By using molecular modeling we demonstrate that both glutamine and its nitro analog in the aci-nitro form participate in the reaction of GTP hydrolysis at the stages of proton transfer and formation of inorganic phosphate. The computed structures and the energy profiles for the complete pathway from the enzyme-substrate to enzyme-product complexes for the wild-type and mutated Ras suggest that the reaction mechanism is not affected by this mutation.
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, 1-3 Leninskie Gory, Moscow, 119991, Russia.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Khrenova
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, 1-3 Leninskie Gory, Moscow, 119991, Russia.|N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 Kosygin Street, Moscow, 119334, Russia.
authors.forename: Bella L
authors.initials: BL
authors.lastname: Grigorenko
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, 1-3 Leninskie Gory, Moscow, 119991, Russia.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Mironov
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, 1-3 Leninskie Gory, Moscow, 119991, Russia.|N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 Kosygin Street, Moscow, 119334, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Nemukhin
mesh_terms: D018698:Glutamic Acid / Q000737:chemistry*; D005973:Glutamine / Q000737:chemistry*; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D006868:Hydrolysis; D009154:Mutation; D018631:ras Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D006160:Guanosine Triphosphate; D018631:ras Proteins
keywords: GTP hydrolysis; QM/MM; Ras-GAP; reaction mechanism; unnatural amino acids