European Biophysics Journal

, Volume 41, Issue 12, pp 1033–1042 | Cite as

Dynamics of heme complexed with human serum albumin: a theoretical approach

  • T. R. Cuya Guizado
  • S. R. W. Louro
  • C. Anteneodo
Original Paper

Abstract

Human serum albumin (HSA) is the most abundant protein in the blood serum. It binds several ligands and has an especially strong affinity for heme, hence becoming a natural candidate for oxygen transport. In order to analyze the interaction of HSA-heme, molecular dynamics simulations of HSA with bound heme were performed. Based on the results of X-ray diffraction, the binding site of the heme, localized in subdomain IB, was considered. We analyzed the fluctuations and their correlations along trajectories to detect collective motions. The role of H bonds and salt bridges in the stabilization of heme in its pocket was also investigated. Complementarily, the localization of water molecules in the hydrophobic pocket and the interaction with heme were discussed.

Keywords

Human serum albumin Heme Molecular dynamics Intermolecular surface contact Molecular latch Collective motions Artificial blood Spatial distribution function 

References

  1. Arnold GE, Ornstein RL (1997) Molecular dynamics study of time-correlated protein motion and molecular flexibility: cytochrome P450BM-3. Biophys J 73:1147–1159PubMedCrossRefGoogle Scholar
  2. Ascenzi P, Bolli A, di Massi A, Tundo GR, Fanali G, Colleta M, Fasano M (2011) Isoniazid and rifampicin inhibit allosterically heme binding to albumin and peroxynitrite isomerization by heme-albumin. Biol Inorg Chem 16:97–108CrossRefGoogle Scholar
  3. Barrett CP, Hall BA, Noble MEM (2004) Dynamite: a simple way to gain insight into protein motions. Acta Cryst D 60:2280–2287CrossRefGoogle Scholar
  4. Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J (1981) In: Pullman B (ed) Intermolecular forces. D. Reidel, DordrechtGoogle Scholar
  5. Berendsen HJC, Postma JPM, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684–3690CrossRefGoogle Scholar
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The Protein Data Bank. Nucleic Acids Res 28:235–242. http://www.pdb.org PubMedCrossRefGoogle Scholar
  7. Bradley MJ, Chivers PT, Baker NA (2008)Molecular dynamics simulation of the Escherichia coli NikR protein: equilibrium conformational fluctuations. J Mol Biol 378:1155–1173PubMedCrossRefGoogle Scholar
  8. Connolly ML (1983) Solvent-accessible surfaces of proteins and nucleic acids. Science 221:709–713PubMedCrossRefGoogle Scholar
  9. Cuya TR, da Rocha Pita S, Louro SRW, Pascutti PG (2008) Computational study of the solvation of protoporphyrin IX and its Fe2+ complex. Int J Quantum Chem 108:2603–2607CrossRefGoogle Scholar
  10. Cuya Guizado TR, Louro SRW, Pascutti PG, Anteneodo C (2010) Solvation of anionic water-soluble porphyrins: a computational study. Int J Quantum Chem 110:2094–2100Google Scholar
  11. Cuya Guizado TR, Louro SRW, Anteneodo CJ (2011) Hydration of hydrophobic biological porphyrins. J Chem Phys 134:(055103)1–9Google Scholar
  12. de Groot BL, van Aalten DMF, Amadei A, Berendsen HJC (1996) The consistency of large concerted motions in proteins in molecular dynamics simulations. Biophys J 71:1707–1713PubMedCrossRefGoogle Scholar
  13. Dockal M, Carter DC, Ruker F (1999) The three recombinant domains of human serum albumin. J Biol Chem 274:29303–29310PubMedCrossRefGoogle Scholar
  14. Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577–8593CrossRefGoogle Scholar
  15. Fujiwara S, Amisaki T (2006) Molecular dynamics study of conformational changes in human serum albumin by binding of fatty acids. Proteins 64:730–739PubMedCrossRefGoogle Scholar
  16. Guex N, Peitsch MC (1997) Swiss-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714–2723PubMedCrossRefGoogle Scholar
  17. Hayward S, Lee RA (2002) Improvements in the analysis of domain motions in proteins from conformational change: DynDom version 1.50. J Mol Graph Model 21:181–183. http://fizz.cmp.uea.ac.uk/dyndom/ PubMedCrossRefGoogle Scholar
  18. Hess B (2000) Similarities between principal components of protein dynamics and random diffusion. Phys Rev E 62:8438–8448CrossRefGoogle Scholar
  19. Horta BAC, Cirino JJV, de Alencastro RB (2007) Dynamical behavior of the vascular endothelial growth factor: biological implications. Proteins 67:517–525PubMedCrossRefGoogle Scholar
  20. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14:33–38PubMedCrossRefGoogle Scholar
  21. Kiselev MA, Gryzunov YA, Dobretsov GE, Komarova MN (2001) Size of a human serum albumin molecule in solution. Biofizika 2001(46):423–427Google Scholar
  22. Komatsu T, Ohmichi N, Zunszain PA, Curry E, Tsuchida E (2004) Dioxygenation of human serum albumin having a prosthetic heme group in a tailor-made heme pocket. J Am Chem Soc 126:14304–14305PubMedCrossRefGoogle Scholar
  23. Komatsu T, Nakagawa A, Zunszain PA, Curry S, Tsuchida E (2007) Genetic engineering of the heme pocket in human serum albumin: modulation of O2 binding of iron protoporphyrin IX by variation of distal amino acids. J Am Chem Soc 129(36):11286–11295PubMedCrossRefGoogle Scholar
  24. Lange OF, Grubmuller H (2006) Generalized correlation for biomolecular dynamics. Proteins 62:1053–1061PubMedCrossRefGoogle Scholar
  25. Lee AL, Wand AJ (2001) Microscopic origins of entropy, heat capacity and the glass transition in proteins. Nature 411:501–504PubMedCrossRefGoogle Scholar
  26. Nelson DL, Cox MM (2000) Principles of biochemistry, 4th edn, p 79Google Scholar
  27. Nocedal J (1980) Updating quasi-Newton matrices with limited storage. Math Comput 35:773–782CrossRefGoogle Scholar
  28. Scheer A, Cotecchia S (1997) Constitutivelt active G protein-coupled receptors: potential mechanisms of receptor activation. J Recept Signal Transduct Res 17:57–73PubMedCrossRefGoogle Scholar
  29. Software developed at the Laboratory of Modeling and Molecular Dynamics of the Biophysics Institute Carlos Chagas Filho - Universidade Federal de Rio de JaneiroGoogle Scholar
  30. Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K (1999) Crystal structure of human serum albumin at 2.5 resolution. Protein Eng 12:439–446PubMedCrossRefGoogle Scholar
  31. van der Spoel D et al (2002) Gromacs user manual. Nijenborgh, Groningen. Available at http://www.gromacs.org
  32. Wang R, Komatsu T, Nakagawa A, Tsuchida E (2005) Human serum albumin bearing covalently attached iron(ii) porphyrins as O2-coordination sites. Bioconj Chem 16:23–26CrossRefGoogle Scholar
  33. Wardell M, Wang Z, Ho JX, Justin R, Ruker F, Ruble J, Carter C (2002) The atomic structure of human serum albumin at 1.9. Biochem Biophys Res Commun 291:813–819PubMedCrossRefGoogle Scholar
  34. Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S (2003) Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. BMC Struct Biol 3:6. Available at http://www.biomedcentral.com/1472-6807/3/6

Copyright information

© European Biophysical Societies' Association 2012

Authors and Affiliations

  • T. R. Cuya Guizado
    • 1
  • S. R. W. Louro
    • 1
  • C. Anteneodo
    • 1
    • 2
  1. 1.Departamento de FísicaPUC-RioRio de JaneiroBrazil
  2. 2.National Institute of Science and Technology for Complex SystemsRio de JaneiroBrazil

Personalised recommendations