2Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, 119994 Moscow, Russia
3Department of Biochemistry, University of Texas, Southwestern Medical Center, 6001 Forest Park, Dallas, Texas, 75390-9050, USA; E-mail: firstname.lastname@example.org
* To whom correspondence should be addressed.
Received September 29, 2008; Revision received October 30, 2008
We compare the computed on the base of quantum mechanical–molecular mechanical (QM/MM) modeling kinetic isotope effects (KIEs) for a series of the 18O-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.
KEY WORDS: kinetic isotope effect, GTP hydrolysis, p21Ras, Ras–GAP, EF-Tu