title: Simulated 18O kinetic isotope effects in enzymatic hydrolysis of guanosine triphosphate.
abstract: We compare the computed on the base of quantum mechanical-molecular mechanical (QM/MM) modeling kinetic isotope effects (KIEs) for a series of the (18)O-labeled substrates in enzymatic hydrolysis of guanosine triphosphate (GTP) with those measured experimentally. Following the quantitative structure-activity relationship concept, we introduce the correlation between KIEs and structure of substrates with the help of a labeling index, which also aids better imaging of presentation of both experimental and theoretical data. An evident correlation of the computed and measured KIEs provides support to the predominantly dissociative-type reaction mechanism of enzymatic GTP hydrolysis predicted in QM/MM simulations.
authors.affiliation: Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia. anemukhin@yahoo.com
authors.forename: A V
authors.initials: AV
authors.lastname: Nemukhin
authors.forename: M S
authors.initials: MS
authors.lastname: Shadrina
authors.forename: B L
authors.initials: BL
authors.lastname: Grigorenko
authors.forename: X
authors.initials: X
authors.lastname: Du
mesh_terms: D004798:Enzymes / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D008958:Models, Molecular; D010103:Oxygen Isotopes / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D004798:Enzymes; D010103:Oxygen Isotopes; D006160:Guanosine Triphosphate