Conformational dynamics of the enzyme-substrate complex of protein kinase A with pseudosubstrate SP20 and adenosine triphosphate
Mulashkina T.I.1 , Leonova M.S.2, Khrenova M.G.3
1. Chemistry Department, Lomonosov Moscow State University, Moscow, Russia 2. Chemistry Department, Lomonosov Moscow State University, Moscow, Russia; Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, Moscow, Russia 3. Chemistry Department, Lomonosov Moscow State University, Moscow, Russia; Bach Institute of Biochemistry, Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences, Moscow, Russia
The phosphorylation reaction, catalyzed by the enzyme protein kinase A (PKA), plays one of the key roles in the work of the glutamatergic system, primarily involved in memory functioning. The analysis of the dynamic behavior of the enzyme-substrate complex allows one to learn the mechanism of the enzymatic reaction. According to the results of classical molecular dynamics calculations followed by hierarchical clustering, the most preferred proton acceptor during the phosphorylation reaction catalyzed by PKA is the carboxyl group of the amino acid residue Asp166; however, the γ-phosphate group of ATP can also act as an acceptor.
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Keywords: protein kinase A, molecular dynamics, conformations, enzyme-substrate complex, ATP
Citation:
Mulashkina T.I., Leonova M.S., Khrenova M.G. (2024) Conformational dynamics of the enzyme-substrate complex of protein kinase A with pseudosubstrate SP20 and adenosine triphosphate. Biomeditsinskaya Khimiya, 70(6), 421-427.
Mulashkina T.I. et al. Conformational dynamics of the enzyme-substrate complex of protein kinase A with pseudosubstrate SP20 and adenosine triphosphate // Biomeditsinskaya Khimiya. - 2024. - V. 70. -N 6. - P. 421-427.
Mulashkina T.I. et al., "Conformational dynamics of the enzyme-substrate complex of protein kinase A with pseudosubstrate SP20 and adenosine triphosphate." Biomeditsinskaya Khimiya 70.6 (2024): 421-427.
Mulashkina, T. I., Leonova, M. S., Khrenova, M. G. (2024). Conformational dynamics of the enzyme-substrate complex of protein kinase A with pseudosubstrate SP20 and adenosine triphosphate. Biomeditsinskaya Khimiya, 70(6), 421-427.
References
Arnsten A.F.T., Wang M. (2020) The evolutionary expansion of mGluR3-NAAG-GCPII signaling: Relevance to human intelligence and cognitive disorders. Am. J. Psychiatry, 177(12), 1103–1106. CrossRef Scholar google search
Gasiorowska A., Wydrych M., Drapich P., Zadrozny M., Steczkowska M., Niewiadomski W., Niewiadomska G. (2021) The biology and pathobiology of glutamatergic, cholinergic, and dopaminergic signaling in the aging brain. Front. Aging Neurosci., 13, 654931. CrossRef Scholar google search
Pang K., Wang W., Qin J.-X., Shi Z.-D., Hao L., Ma Y.-Y., Xu H., Wu Z.-H., Pan D., Chen Z.-S., Han C.-H. (2022) Role of protein phosphorylation in cell signaling, disease, and the intervention therapy. MedComm, 3(4), e175. CrossRef Scholar google search
Gerlits O., Waltman M.J., Taylor S., Langan P., Kovalevsky A. (2013) Insights into the phosphoryl transfer catalyzed by cAMP-dependent protein kinase:An X-ray crystallographic study of complexes with various metals and peptide substrate SP20. Biochemistry, 52(21), 3721–3727. CrossRef Scholar google search
Johnson D.A., Akamine P., Radzio-Andzelm E., Madhusudan M., Taylor S.S. (2001) Dynamics of cAMP-dependent protein kinase. Chem. Rev., 101(8), 2243–2270. CrossRef Scholar google search
Adams J.A. (2001) Kinetic and catalytic mechanisms of protein kinases. Chem. Rev., 101(8), 2271–2290. CrossRef Scholar google search
Taylor S.S., Yang J., Wu J., Haste N.M., Radzio-Andzelm E., Anand G. (2004) PKA: Aportrait of protein kinase dynamics. Biochim. Biophys. Acta, 1697(1–2), 259–269. CrossRef Scholar google search
Word J.M., Lovell S.C., Richardson J.S., Richardson D.C. (1999) Asparagine and glutamine: Using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol., 285(4), 1735–1747. CrossRef Scholar google search
Humphrey W., Dalke A., Schulten K. (1996) VMD: Visual molecular dynamics. J. Mol. Graph., 14(1), 33–38. CrossRef Scholar google search
Phillips J.C., Braun R., Wang W., Gumbart J., Tajkhorshid E., Villa E., Chipot C., Skeel R.D., Kalé L., Schulten K. (2005) Scalable molecular dynamics with NAMD. J. Comput. Chem., 26(16), 1781–1802. CrossRef Scholar google search
Best R.B., Zhu X., Shim J., Lopes P.E.M., Mittal J., Feig M., MacKerell A.D. (2012) Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ1 and χ2 dihedral angles. J. Chem. Theory Comput., 8, 3257–3273.
