Conformational particularities of beta-amyloid peptide 25-35

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Somente assinantes

Resumo

In Alzheimer's disease, beta-amyloid peptide (Ав) plays an important role in the mechanism of neurodegeneration. A small fragment of Лв(25-35) (with the sequence GSNKGAIIGLLM) is regarded to be the functional domain of Лв, responsible for its neurotoxic properties and represents the biological active region of Лв. Conformational analysis of each C-terminal segment of the peptide by the method of molecular mechanics revealed a limited number of most probable conformations and quite clearly helped to clarify what forces stabilize the structures. The obtained results showed that Лв(25-35) energetically has a propensity for adopting alpha-helix conformation of the C-terminal octapeptide segment. A molecular dynamics method was used to build a model of intramolecular mobility in the Лв(25-35) molecule. It was demonstrated that in low-energy conformations, Лв(25-35), the orientation of flexible structures of the N-terminal region with respect to the structures of the C-terminal region is different.

Sobre autores

G. Agaeva

Baku State University

Email: gulshen@mail.ru
Baku, Azerbaijan

G. Najafova

French-Azerbaijani University

Baku, Azerbaijan

Bibliografia

  1. L. N. Zhao, L. Lu, L. Y. Chew, and Y. Mu, Int. J. Mol. Sci., 15, 12631 (2014).
  2. E. Cerf, R. Sarroukh, S. Tamamizu-Kato, et al., Biochem. J., 421, 415 (2009).
  3. R. Sultana, H. F. Poon, J. Cai, et al., Neurobiol. Dis., 22, 76 (2006).
  4. T. Kohno, K. Kobayashi, T. Maeda, et al., Biochemistry, 35, 16094 (1996).
  5. M. Coles, W. Bicknell, A. A. Watson, et al., Biochemistry, 37, 11064 (1998).
  6. O. M. A. El-Agnaf, G. B. Irvine, G. Fitzpatrick, et al., Biochem. J., 336 (Pt 2), 419 (1998)
  7. G. Shanmugam and R. Jayakumar, Biopolymers, 33, 421 (2004).
  8. G. Shanmugam, P. L. Polavarapu, Biophys. J., 87, 622 (2004).
  9. A. M. D'Ursi, M. R. Armenante, R. Guerrini, et al., J. Med. Chem, 12, 4231 (2004).
  10. G. Wei and J. E. Shea, Biophys. J., 91, 1638 (2006).
  11. S. Lee and Y. Kim, Bull. Korean Chem. Soc., 25, 838 (2004).
  12. L. Millucci, L. Ghezzi, G. Bernardini, and A. Santucci, Curr. Prot. Peptide Sci., 11, 54 (2010).
  13. B. Ma and R. Nussinov, Biophys. J., 90, 3365 (2006).
  14. E. Terzi, G. Holzemann, and J. Seelig, Biochemistry, 33, 1345 (1994).
  15. Y. Song, P. Li, L. Liu, et al., Sci. Rep., 8, 765 (2018).
  16. R. F. McGuire, F. A. Momany, and H. A. Scheraga, J. Phys. Chem., 76, 375 (1972).
  17. F. A. Momany, R. F. McGuire, A. W. Burgess, and H. A. Scheraga, J. Phys. Chem., 79, 2361 (1975).
  18. H.A. Scheraga, Biopolymers, 22, 1 (1983).
  19. G. Nemethy, M. S. Pottle, and H. A. Scheraga, J. Phys. Chem., 87, 1883 (1983).
  20. E. M. Popov, Int. J. Quant. Chem., 16, 707 (1979).
  21. I. S. Maksumov, L. I. Ismailova, and N. M. Godjaev, J. Sruct. Khim., 24, 147 (1983).
  22. J. Jr. Hermans and D. Ferro, Biopolymers, 10, 1121 (1971).
  23. W. C. Davidon, AEC Res. Develop. Rep., ANL-5990 (1959).
  24. R. Fletcher and M. J. D. Powell, J.Computer, 6, 163 (1963).
  25. IUPAC-IUB Commission on Biochemical Nomenclature Abbreviations and symbols for description of conformation of polypeptide chains, Pure Appl. Chem., 40, 291 (1974).
  26. S. Weiner, P. Kollman, D. T. Nguyen, and D. A. Case, J.Comput. Chem., 7, 230 (1986).
  27. N. L. Allinger and Y. Yuh, MM2 Program, QCPE 395 (Indiana University, Indiana, 1982).
  28. D. White, J. Kuddock, and P. Edgington, in CHEM-MIN Program in Computer Aided Molecular Design, Ed. by W. G. Richards (IBC Technical Services, 1989).
  29. W. C. Still, MacroModel (Columbia University, NY, USA).
  30. Quanta/CHARMm, Molecular Simulations (Warmshurst, Mass., USA).
  31. J. W. Pitera, M. Falta, and W. F. van Gunsteren, Biophys. J., 80, 2546 (2001).
  32. G. A. Agaeva, U. T. Agaeva, and N. M. Godjaev, Biophysics (Springer), 60, 365 (2015).
  33. M. D. Kirkitadze, M. M. Condron, and D. B. Teplow, J. Mol. Biol., 312, 1103 (2001).
  34. Y. Fezoui, D. M. Hartley, D. M. Walsh, et al., Nature Struct. Biol, 7, 1095 (2000).

Declaração de direitos autorais © Russian Academy of Sciences, 2023

Este site utiliza cookies

Ao continuar usando nosso site, você concorda com o procedimento de cookies que mantêm o site funcionando normalmente.

Informação sobre cookies