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. 2002 Dec;83(6):3049–3065. doi: 10.1016/S0006-3495(02)75310-1

Molecular dynamics study of Desulfovibrio africanus cytochrome c3 in oxidized and reduced forms.

Céline Bret 1, Michel Roth 1, Sofie Nørager 1, E Claude Hatchikian 1, Martin J Field 1
PMCID: PMC1302385  PMID: 12496077

Abstract

A 5-ns molecular dynamics study of a tetraheme cytochrome in fully oxidized and reduced forms was performed using the CHARMM molecular modeling program, with explicit water molecules, Langevin dynamics thermalization, Particle Mesh Ewald long-range electrostatics, and quantum mechanical determination of heme partial charges. The simulations used, as starting points, crystallographic structures of the oxidized and reduced forms of the acidic cytochrome c(3) from Desulfovibrio africanus obtained at pH 5.6. In this paper we also report structures for the two forms obtained at pH 8. In contrast to previous cytochrome c(3) dynamics simulations, our model is stable. The simulation structures agree reasonably well with the crystallographic ones, but our models show higher flexibility and the water molecules are more labile. We have compared in detail the differences between the simulated and experimental structures of the two redox states and observe that the hydration structure is highly dependent on the redox state. We have also analyzed the interaction energy terms between the hemes, the protein residues, and water. The direct electrostatic interaction between hemes is weak and nearly insensitive to the redox state, but the remaining terms are large and contribute in a complex way to the overall potential energy differences that we see between the redox states.

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Selected References

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  1. Antosiewicz J., McCammon J. A., Gilson M. K. Prediction of pH-dependent properties of proteins. J Mol Biol. 1994 May 6;238(3):415–436. doi: 10.1006/jmbi.1994.1301. [DOI] [PubMed] [Google Scholar]
  2. Baptista A. M., Martel P. J., Soares C. M. Simulation of electron-proton coupling with a Monte Carlo method: application to cytochrome c3 using continuum electrostatics. Biophys J. 1999 Jun;76(6):2978–2998. doi: 10.1016/S0006-3495(99)77452-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berman H. M., Westbrook J., Feng Z., Gilliland G., Bhat T. N., Weissig H., Shindyalov I. N., Bourne P. E. The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235–242. doi: 10.1093/nar/28.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brennan L., Turner D. L., Messias A. C., Teodoro M. L., LeGall J., Santos H., Xavier A. V. Structural basis for the network of functional cooperativities in cytochrome c(3) from Desulfovibrio gigas: solution structures of the oxidised and reduced states. J Mol Biol. 2000 Apr 21;298(1):61–82. doi: 10.1006/jmbi.2000.3652. [DOI] [PubMed] [Google Scholar]
  5. Friesner R. A. New methods for electronic structure calculations on large molecules. Annu Rev Phys Chem. 1991;42:341–367. doi: 10.1146/annurev.pc.42.100191.002013. [DOI] [PubMed] [Google Scholar]
  6. García A. E., Hummer G. Water penetration and escape in proteins. Proteins. 2000 Feb 15;38(3):261–272. [PubMed] [Google Scholar]
  7. Gilson M. K. Multiple-site titration and molecular modeling: two rapid methods for computing energies and forces for ionizable groups in proteins. Proteins. 1993 Mar;15(3):266–282. doi: 10.1002/prot.340150305. [DOI] [PubMed] [Google Scholar]
  8. Gordon E. H., Pike A. D., Hill A. E., Cuthbertson P. M., Chapman S. K., Reid G. A. Identification and characterization of a novel cytochrome c(3) from Shewanella frigidimarina that is involved in Fe(III) respiration. Biochem J. 2000 Jul 1;349(Pt 1):153–158. doi: 10.1042/0264-6021:3490153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jones T. A., Zou J. Y., Cowan S. W., Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991 Mar 1;47(Pt 2):110–119. doi: 10.1107/s0108767390010224. [DOI] [PubMed] [Google Scholar]
  10. Lounnas V., Pettitt B. M., Phillips G. N., Jr A global model of the protein-solvent interface. Biophys J. 1994 Mar;66(3 Pt 1):601–614. doi: 10.1016/s0006-3495(94)80835-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Louro R. O., Bento I., Matias P. M., Catarino T., Baptista A. M., Soares C. M., Carrondo M. A., Turner D. L., Xavier A. V. Conformational component in the coupled transfer of multiple electrons and protons in a monomeric tetraheme cytochrome. J Biol Chem. 2001 Sep 10;276(47):44044–44051. doi: 10.1074/jbc.M107136200. [DOI] [PubMed] [Google Scholar]
  12. Magro V., Pieulle L., Forget N., Guigliarelli B., Petillot Y., Hatchikian E. C. Further characterization of the two tetraheme cytochromes c3 from Desulfovibiro africanus: nucleotide sequences, EPR spectroscopy and biological activity. Biochim Biophys Acta. 1997 Oct 17;1342(2):149–163. doi: 10.1016/s0167-4838(97)00096-4. [DOI] [PubMed] [Google Scholar]
  13. Martel P. J., Soares C. M., Baptista A. M., Fuxreiter M., Náray-Szabó G., Louro R. O., Carrondo M. A. Comparative redox and pKa calculations on cytochrome c3 from several Desulfovibrio species using continuum electrostatic methods. J Biol Inorg Chem. 1999 Feb;4(1):73–86. doi: 10.1007/s007750050291. [DOI] [PubMed] [Google Scholar]
  14. Nørager S., Legrand P., Pieulle L., Hatchikian C., Roth M. Crystal structure of the oxidised and reduced acidic cytochrome c3from Desulfovibrio africanus. J Mol Biol. 1999 Jul 23;290(4):881–902. doi: 10.1006/jmbi.1999.2917. [DOI] [PubMed] [Google Scholar]
  15. Pereira Patrícia M., Pacheco Isabel, Turner David L., Louro Ricardo O. Structure-function relationship in type II cytochrome c(3) from Desulfovibrio africanus: a novel function in a familiar heme core. J Biol Inorg Chem. 2002 Apr 27;7(7-8):815–822. doi: 10.1007/s00775-002-0364-0. [DOI] [PubMed] [Google Scholar]
  16. Pessanha M., Brennan L., Xavier A. V., Cuthbertson P. M., Reid G. A., Chapman S. K., Turner D. L., Salgueiro C. A. NMR structure of the haem core of a novel tetrahaem cytochrome isolated from Shewanella frigidimarina: identification of the haem-specific axial ligands and order of oxidation. FEBS Lett. 2001 Jan 26;489(1):8–13. doi: 10.1016/s0014-5793(00)02383-8. [DOI] [PubMed] [Google Scholar]
  17. Pieulle L., Haladjian J., Bonicel J., Hatchikian E. C. Biochemical studies of the c-type cytochromes of the sulfate reducer Desulfovibrio africanus. Characterization of two tetraheme cytochromes c3 with different specificity. Biochim Biophys Acta. 1996 Jan 11;1273(1):51–61. doi: 10.1016/0005-2728(95)00129-8. [DOI] [PubMed] [Google Scholar]
  18. Salgueiro C. A., da Costa P. N., Turner D. L., Messias A. C., van Dongen W. M., Saraiva L. M., Xavier A. V. Effect of hydrogen-bond networks in controlling reduction potentials in Desulfovibrio vulgaris (Hildenborough) cytochrome C3 probed by site-specific mutagenesis. Biochemistry. 2001 Aug 14;40(32):9709–9716. doi: 10.1021/bi010330b. [DOI] [PubMed] [Google Scholar]
  19. Soares C. M., Martel P. J., Mendes J., Carrondo M. A. Molecular dynamics simulation of cytochrome c3: studying the reduction processes using free energy calculations. Biophys J. 1998 Apr;74(4):1708–1721. doi: 10.1016/S0006-3495(98)77882-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sterpone F., Ceccarelli M., Marchi M. Dynamics of hydration in hen egg white lysozyme. J Mol Biol. 2001 Aug 10;311(2):409–419. doi: 10.1006/jmbi.2001.4860. [DOI] [PubMed] [Google Scholar]
  21. Teixeira Vitor H., Soares Cláudio M., Baptista António M. Studies of the reduction and protonation behavior of tetraheme cytochromes using atomic detail. J Biol Inorg Chem. 2001 Sep 20;7(1-2):200–216. doi: 10.1007/s007750100287. [DOI] [PubMed] [Google Scholar]
  22. Valente F. M., Saraiva L. M., LeGall J., Xavier A. V., Teixeira M., Pereira I. A. A membrane-bound cytochrome c3: a type II cytochrome c3 from Desulfovibrio vulgaris Hildenborough. Chembiochem. 2001 Dec 3;2(12):895–905. doi: 10.1002/1439-7633(20011203)2:12<895::AID-CBIC895>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]

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