Molecular polymorphism of human enzymes as the basis of individual sensitivity to drugs. Supercomputer-assisted modeling as a tool for analysis of structural changes and enzymatic activity of proteins
- Autores: Varfolomeev S.1,2, Lushchekina S.1, Nemukhin A.1,2, Kulakova A.2, Kots E.1,2, Makhaeva G.3, Delacour H.4, Lockridge O.5, Masson P.6
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Afiliações:
- N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences
- Department of Chemistry, M. V. Lomonosov Moscow State University
- Institute of Physiologically Active Compounds, Russian Academy of Sciences
- Department of Biology, Bégin Military Teaching Hospital
- University of Nebraska Medical Center, Eppley Institute
- Kazan (Volga region) Federal University
- Edição: Volume 65, Nº 6 (2016)
- Páginas: 1592-1607
- Seção: Full Articles
- URL: https://journals.rcsi.science/1066-5285/article/view/238443
- DOI: https://doi.org/10.1007/s11172-016-1487-8
- ID: 238443
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Resumo
The nature of individual sensitivity to drugs associated with molecular polymorphism of human enzymes is discussed. The influence of molecular polymorphism on the activity of key human esterases, in particular, cholinesterases and carboxylesterase, responsible for hydrolytic metabolism of ester-containing drugs, is analyzed. A method was developed, which involves supercomputer-assisted modeling as a tool for assessment of molecular mechanism of the impact of point mutations on the catalytic activity of enzymes. This work is a part of a study aimed at elaboration of the concept and methods of personalized medicine.
Sobre autores
S. Varfolomeev
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences; Department of Chemistry, M. V. Lomonosov Moscow State University
Autor responsável pela correspondência
Email: sdvarf@sky.chph.ras.ru
Rússia, 4 ul. Kosygina, Moscow, 119334; Build. 3,1 Leninskie Gory, Moscow, 119991
S. Lushchekina
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences
Email: sdvarf@sky.chph.ras.ru
Rússia, 4 ul. Kosygina, Moscow, 119334
A. Nemukhin
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences; Department of Chemistry, M. V. Lomonosov Moscow State University
Email: sdvarf@sky.chph.ras.ru
Rússia, 4 ul. Kosygina, Moscow, 119334; Build. 3,1 Leninskie Gory, Moscow, 119991
A. Kulakova
Department of Chemistry, M. V. Lomonosov Moscow State University
Email: sdvarf@sky.chph.ras.ru
Rússia, Build. 3,1 Leninskie Gory, Moscow, 119991
E. Kots
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences; Department of Chemistry, M. V. Lomonosov Moscow State University
Email: sdvarf@sky.chph.ras.ru
Rússia, 4 ul. Kosygina, Moscow, 119334; Build. 3,1 Leninskie Gory, Moscow, 119991
G. Makhaeva
Institute of Physiologically Active Compounds, Russian Academy of Sciences
Email: sdvarf@sky.chph.ras.ru
Rússia, 1 Severnyi proezd, Chernogolovka, Moscow Region, 142432
H. Delacour
Department of Biology, Bégin Military Teaching Hospital
Email: sdvarf@sky.chph.ras.ru
França, 69 Paris Av. 94 163, Saint Mandé
O. Lockridge
University of Nebraska Medical Center, Eppley Institute
Email: sdvarf@sky.chph.ras.ru
Estados Unidos da América, Omaha, NE, 68198-5950
P. Masson
Kazan (Volga region) Federal University
Email: sdvarf@sky.chph.ras.ru
Rússia, 18 ul. Kremlevskaya, Kazan, 420008