Molecular Oxygen Migration in the Isolated β Chains of Human Hemoglobin as Revealed by Molecular Dynamics Simulations and Laser Kinetic Spectroscopy

Molecular dynamics simulations and laser kinetic absorption spectroscopy have been used to study the molecular oxygen (O₂) migration in the isolated β chains of human hemoglobin. The insertion of xenon (Xe) atoms into the isolated chains has been found to decrease the time constant of the slowest component of the geminate O₂ rebinding to the protein. This change is caused by a decrease in an intra-protein space available for the O₂ migration after the insertion of the inert gas into the Xe-binding sites of the protein. The molecular dynamics simulations have revealed that during the course of the geminate recombination to the isolated β-chains, the O₂ molecule visits both Xe2 and Xe1 site of the protein. The amino acids involved in the formation of the primary and secondary docking sites of the protein have been determined. The obtained results are important for understanding the mechanism of O₂ binding by both native tetrameric human hemoglobin and artificial oxygen carriers based on heme proteins.

1. E. Antonini, M. Brunori. Hemoglobin and Myoglobin in their Reactions with Ligands, North-Holland Publication Company, Amsterdam, London (1971)

2. M. F. Perutz. Nature, 228 (1970) 726—739

3. Q. H. Gibson. Biochem. J., 71 (1959) 293—303

4. J. S. Philo, J. W. Lary. J. Biol. Chem., 265 (1990) 139—143

5. I. Birukou, R. L. Schweers, J. S. Olson. J. Biol. Chem., 285 (2010) 8840—8854

6. S. V. Lepeshkevich, N. V. Konovalova, B. M. Dzhagarov. Biochem. Mos., 68, N 5 (2003) 551—558

7. B. M. Dzhagarov, S. V. Lepeshkevich. Chem. Phys. Lett., 390, N 1-3 (2004) 59—64

8. S. V. Lepeshkevich, N. V. Konovalova, I. I. Stepuro, B. M. Dzhagarov. J. Mol. Struct., 735-736 (2005) 307—313

9. S. V. Lepeshkevich, B. M. Dzhagarov. FEBS J., 272, N 23 (2005) 6109—6119

10. D. A. Duddell, R. J. Morris, N. J. Muttucumaru, J. T. Richards. Photochem. Photobiol., 31 (1980) 479—484

11. R. J. Morris, Q. H. Gibson, M. Ikeda-Saito, T. Yonetani. J. Biol. Chem., 259 (1984) 6701—6703

12. D. A. Chernoff, R. M. Hochstrasser, A. W. Steele. Proc. Natl. Acad. Sci. U.S.A., 77 (1980) 5606—5610

13. B. M. Dzhagarov, V. A. Galievsky, N. N. Kruk, M. D. Yakutovich. Dokl. Akad. Nauk, 366 (1999) 38—41

14. S. V. Lepeshkevich, J. Karpiuk, I. V. Sazanovich, B. M. Dzhagarov. Biochemistry, 43, N 6 (2004) 1675—1684

15. Q. H. Gibson. Biochemistry, 38, N 16 (1999) 5191—5199

16. W. A. Eaton, L. K. Hanson, P. J. Stephens, J. C. Sutherland, J. B. R. Dunn. J. Am. Chem. Soc., 100, N 16 (1978) 4991—5003

17. B. I. Greene, R. M. Hochstrasser, R. B. Weisman, W. A. Eaton. Proc. Natl. Acad. Sci. U.S.A., 75, N 11 (1978) 5255—5259

18. S. V. Lepeshkevich, I. V. Sazanovich, M. V. Parkhats, S. N. Gilevich, B. M. Dzhagarov. Chem. Sci., 12, N 20 (2021) 7033—7047

19. A. Pesce, M. Nardini, S. Dewilde, L. Capece, M. A. Marti', S. Congia, M. D. Salter, G. C. Blouin, D. A. Estrin, P. Ascenzi, L. Moens, M. Bolognesi, J. S. Olson. J. Biol. Chem., 286 (2011) 5347—5358

20. B. A. Springer, S. G. Sligar, J. S. Olson, G. N. Phillips Jr. Chem. Rev., 94 (1994) 699—714

21. J. M. Friedman. Science, 228 (1985) 1273—1280

22. C. Savino, A. E. Miele, F. Draghi, K. A. Johnson, G. Sciara, M. Brunori, B. Vallone. Biopolymers, 91, N 12 (2009) 1097—1107

23. S. V. Lepeshkevich, S. A. Biziuk, A. M. Lemeza, B. M. Dzhagarov. Biochim. Biophys. Acta, 1814, N 10 (2011) 1279—1288

24. M. F. Lucas, V. Guallar. Biophys. J., 102 (2012) 887—896

25. M. S. Shadrina, G. H. Peslherbe, A. M. English. Biochemistry, 54 (2015) 5268—5278

26. M. S. Shadrina, A. M. English, G. H. Peslherbe. J. Am. Chem. Soc., 134 (2012) 11177—11184

27. M. Takayanagi, I. Kurisaki, M. Nagaoka. J. Phys. Chem. B, 117 (2013) 6082—6091

28. S. V. Lepeshkevich, S. N. Gilevich, M. V. Parkhats, B. M. Dzhagarov. Biochim. Biophys. Acta, 1864, N 9 (2016) 1110—1121

29. E. Bucci, C. Fronticelli. J. Biol. Chem., 240 (1965) 551—552

30. R. C. Neuman Jr., W. Kauzmann, A. Zipp. J. Phys. Chem., 77 (1973) 2687—2691

31. S. V. Lepeshkevich, B. M. Dzhagarov. Biochim. Biophys. Acta, 1794 (2009) 103—109

32. S. V. Lepeshkevich, M. V. Parkhats, A. S. Stasheuski, V. V. Britikov, E. S. Jarnikova, S. A. Usanov, B. M. Dzhagarov. J. Phys. Chem. A, 118, N 10 (2014) 1864—1878

33. S. V. Lepeshkevich, A. L. Poznyak, B. M. Dzhagarov. J. Appl. Spectr., 72, N 5 (2005) 735—743

34. S. V. Lepeshkevich, M. V. Parkhats, I. I. Stepuro, B. M. Dzhagarov. Biochim. Biophys. Acta, 1794, N 12 (2009) 1823—1830

35. H. J. C. Berendsen, D. Van der Spoel, R. Van Drunen. Comp. Phys. Commun., 91 (1995) 43—56

36. D. Van der Spoel, E. Lindahl, B. Hess, G. Groenhof, A. E. Mark, H. J. C. Berendsen. J. Comp. Chem., 26 (2005) 1701—1719

37. E. Lindahl, B. Hess, D. Van der Spoel. J. Mol. Mod., 7 (2001) 306—317

38. W. Humphrey, A. Dalke, K. Schulten. J. Mol. Graphics, 14 (1996) 33—38

39. Y. Cheng, T.-J. Shen, V. Simplaceanu, C. Ho. Biochemistry, 41 (2002) 11901—11913

40. I. Birukou, J. Soman, J. S. Olson. J. Biol. Chem., 286 (2011) 10515—10529