Biochemistry (Moscow)

, Volume 74, Issue 9, pp 1044–1048 | Cite as

Simulated 18O kinetic isotope effects in enzymatic hydrolysis of guanosine triphosphate

  • A. V. NemukhinEmail author
  • M. S. Shadrina
  • B. L. Grigorenko
  • X. Du


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 



elongation factor Tu


enzyme-substrate complex


kinetic isotope effect


quantum mechanical-molecular mechanical method


transition state


zero point energies


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Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  • A. V. Nemukhin
    • 1
    • 2
    Email author
  • M. S. Shadrina
    • 1
  • B. L. Grigorenko
    • 1
  • X. Du
    • 3
  1. 1.Faculty of ChemistryLomonosov Moscow State UniversityMoscowRussia
  2. 2.Emanuel Institute of Biochemical PhysicsRussian Academy of SciencesMoscowRussia
  3. 3.Department of BiochemistryUniversity of Texas, Southwestern Medical CenterDallasUSA

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