Molecular dynamics simulations of a DNA photolyase protein: High-mobility and conformational changes of the FAD molecule at low temperatures

DOI: 10.4236/abb.2012.33025   PDF   HTML     4,856 Downloads   8,839 Views   Citations


A molecular dynamics (MD) simulation is performed on a DNA photolyase to study the conformational behavior of the photoactive cofactor flavin adenine dinucleotide (FAD) inside the enzyme pocket. A DNA photolyase is a highly efficient light-driven enzyme that repairs the UV-induced cyclobutane pyrimidine dimer in damaged DNA. In this work, the FAD conformational and dynamic changes were studied within the total complex structure of a DNA photolyase protein (containing FADH–, MTHF, and DNA molecules) embedded in a water solvent. We aimed to compare the conformational changes of the FAD cofactor and other constituent fragments of the molecular system under consideration. The obtained results were discussed to gain insight into the light-driven mechanism of DNA repair by a DNA photolyase enzyme—based on the enzyme structure, the FAD mobility, and conformation shape.

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Kholmurodov, K. , Dushanov, E. and Yasuoka, K. (2012) Molecular dynamics simulations of a DNA photolyase protein: High-mobility and conformational changes of the FAD molecule at low temperatures. Advances in Bioscience and Biotechnology, 3, 169-180. doi: 10.4236/abb.2012.33025.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Sancar, A. (2003) Structure and function of DNA Photolyase and cryptochrome blue-light photoreceptors. Chemical Reviews, 103, 2203-2237. doi:10.1021/cr0204348
[2] Tamada, T., Kitadokoro, K., Higuchi, Y., Inaka, K., Yasui, A., de Ruiter, P.E., Eker, A.P. and Miki, K. (1997) Crystal structure of DNA photolyase from Anacystis nidulans. Nature Structural & Molecular Biology, 4, 887-891. doi:10.1038/nsb1197-887
[3] Antony, J., Medvedev, D. and Stuchebrukhov, A. (2000) Theoretical study of electron transfer between the photolyase catalytic cofactor FADH– and DNA thymine dimmer. Journal of American Chemical Society, 122, 1057-1065. doi:10.1021/ja993784t
[4] Mees, A., Klar, T., Gnau, P., Hennecke, U., Eker, A.P.M., Carell, T. and Essen, L.-O. (2004) Crystal structure of a photolyase bound to a CPD-Like DNA lesion after in situ repair. Science, 306, 1724. doi:10.1126/science.1101598
[5] Oberpichler, I., Pierik, A., Wesslowski, J., Pokorny, R., Rosen, R., Vugman, M., Zhang, F., Neubauer, O., Ron, E., Batschauer, A. and Lamparter, T. (2011) A photolyase-like protein from Agrobacterium tumefaciens with an iron-sulfur cluster. PLoS ONE, 6, e26775. doi:10.1371/journal.pone.0026775
[6] Lucas-Lledó, J.I. and Lynch, M. (2009) Evolution of mutation rates: Phylogenomic analysis of the photolyase/ cryptochrome family. Molecular Biology and Evolution, 26, 1143-1153. doi:10.1093/molbev/msp029
[7] Selby, C.P. and Sancar, A. (2006) A cryptochrome/ photolyase class of enzymes with single-stranded DNA- specific photolyase activity. PNAS, 103, 17696-17700. doi:10.1073/pnas.0607993103
[8] Liu, F., Ye, X.-S., Wu, T., Wang, C.-T., Shen, J.-W. and Kang, Y. (2008) Conformational mobility of GOx coenzyme complex on single-wall carbon nanotubes. Sensors, 8, 8453-8462. doi:10.3390/s8128453
[9] Hahn, J., Michel-Beyerle, M.-E. and R?sch, N. (1998) Conformation of the flavin adenine dinucleotide cofactor FAD in DNA-Photolyase: A molecular dynamics study. Journal of Molecular Modeling, 4, 73-82. doi:10.1007/s008940050133
[10] Karplus, P.A. and Schulz, G.E. (1987) Refined structure of glutathione reductase at 1.54 ? resolution. Journal of Molecular Biology, 195, 701-729. doi:10.1016/0022-2836(87)90191-4
[11] Thompson, C.L. and Sancar, A. (2002) Photolyase/cryptochrome blue-light photoreceptors use photon energy to repair DNA and reset the circadian clock. Oncogene, 21, 9043-9056. doi:10.1038/sj.onc.1205958
[12] Verma, P.K. and Pal, S.K. (2010) Ultrafast resonance energy transfer in bio-molecular systems. The European Physical Journal D, 60, 137-156. doi:10.1140/epjd/e2010-00107-7
[13] Park, H.-W., Kim, S.-T., Sancar, A. and Deisenhofer, J. (1995) Crystal structure of DNA photolyase from Es-cherichia coli. Science, 268, 1866. doi:10.1126/science.7604260
[14] Luo, G.B., Andricioaei, I., Xie, X.S. and Karplus, M., (2006) Dynamic distance disorder in proteins is caused by trapping. Journal of Physical Chemistry B, 110, 9363- 9367. doi:10.1021/jp057497p
[15] Wang, Y., Gasper, P.P. and Taylor, J.S. (2000) Quantum chemical study of the electron-transfer-catalyzed splitting of oxetane and azetidine intermediates proposed in the photoenzymatic repair of (6 - 4) Photoproducts of DNA. Journal of American Chemical Society, 122, 5510. doi:10.1021/ja992244t
[16] Masson, F., Laino, T., Rothlisberger, U. and Hutter, J. (2009) A QM/MM investigation of thymine dimer radical anion splitting catalyzed by DNA Photolyase. Chemical Physics and Physical Chemistry, 10, 400-410.
[17] Pearlman, D.A., Case, D.A., Caldwell, J.W., Ross, W.R., Cheatham, T.E., DeBolt, S., Ferguson, D., Seibel, G. and Kollman, P. (1995) AMBER, a computer program for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to elucidate the structures and energies of molecules. Computer Physics Communications, 91, 1-41. doi:10.1016/0010-4655(95)00041-D
[18] Case, D.A., Cheatham, T., Darden, T., Gohlke, H., Luo, R., Merz, K.M. Jr., Onufriev, A., Simmerling, C., Wang, B. and Woods, R. (2005) The Amber biomolecular simulation programs. Journal of Computational Chemistry, 26, 1668-1688. doi:10.1002/jcc.20290
[19] Essmann, U., Perera, L., Berkowitz, M.L., Darden, T., Lee, H. and Pedersen, L.G. (1995) A smooth particle mesh Ewald method. Journal of Chemical Physics, 103, 8577-8592. doi:10.1063/1.470117
[20] Kholmurodov, K., Smith, W., Yasuoka, K., Darden, T. and Ebisuzaki, T.J. (2000) A smooth-particle mesh Ewald method for DL_POLY molecular dynamics simulation package on the Fujitsu VPP700. Journal of Computational Chemistry, 21, 1187-1191. doi:10.1002/1096-987X(200010)21:13<1187::AID-JCC7>3.0.CO;2-7
[21] Ponder, J.W. and Case, D.A. (2003) Force fields for protein simulations. Advances in Protein Chemistry, 66, 27- 85. doi:10.1016/S0065-3233(03)66002-X
[22] Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Jr. Merz, K.M., Ferguson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, J.W. and Kollman, P.A. (1995) A second generation forth field for the simulation of proteins and nucleic acids. Journal of American Chemical Society, 117, 5179-5197. doi:10.1021/ja00124a002
[23] Jorgensen, W.L., Chandrasekhar, J. and Madura, J.D. (1983) Comparison of simple potential functions for simu- lating liquid water. Journal of Chemical Physics, 79, 926- 935. doi:10.1063/1.445869
[24] Berendsen, H.J.C., Postma, J.P.M., van Gunsteren, W.F., DiNola, A. and Haak, J.R. (1984) Molecular dynamics with coupling to an external bath. Journal of Chemical Physics, 81, 3684-3690. doi:10.1063/1.448118
[25] Ryckaert, J.P., Ciccotti, G. and Berendsen, H.J.C. (1997) Numerical integration of the Cartesian equations of proteins and nucleic acids. Journal of Computational Physics, 23, 327-341. doi:10.1016/0021-9991(77)90098-5
[26] Sayle, R.A. and Milner-White, E.J. (1995) RasMol: Biomolecular graphics for all. Trends in Biochemical Sciences, 20, 374-376. doi:10.1016/S0968-0004(00)89080-5
[27] Koradi, R., Billeter, M. and Wuthrich, K. (1996) MOL- MOL: A program for display and analysis of macromo-lecular structure. Journal of Molecular Graphics, 4, 51- 55. doi:10.1016/0263-7855(96)00009-4
[28] Humphrey, W., Dalke, A. and Schulten, K. (1996) VMD —Visual molecular dynamics. Journal of Molecular Graphics, 14, 33-38. doi:10.1016/0263-7855(96)00018-5
[29] Mirzadegan, T., Benko, G., Filipek, S. and Palczewski, K. (2003) Sequence analyses of G-protein-coupled receptors: Similarities to rhodopsin. Biochemistry, 42, 2759-2767. doi:10.1021/bi027224+
[30] Gether, U. and Kobilka, B.K. (1998) G protein-coupled receptor. The Journal of Biological Chemistry, 273, 17979-17982. doi:10.1074/jbc.273.29.17979
[31] Palczewski, K., Kumasaka, T., Hori, T., Behnke, C.A., Motoshima, H., Fox, B.A., Le Trong, I., Teller, D.C., Okada, T., Stenkamp, R.E., Yamamoto, M. and Miyano, M. (2000) Crystal structure of rhodopsin: A G protein- coupled receptor. Science, 289, 739-745. doi:10.1126/science.289.5480.739
[32] Okada, T., Sugihara, M., Bondar, A.-N., Elstner, M., Entel, P. and Buss, V. (2004) The retinal conformation and its environment in rhodopsin in light of a new 2.2 ? crystal structure. Journal of Molecular Biology, 342, 571-583. doi:10.1016/j.jmb.2004.07.044
[33] Salgado, G.F.J., Struts, A.V., Tanaka, K., Fujioka, N., Nakanishi, K. and Brown, M.F. (2004) Deuterium NMR structure of retinal in the ground state of rhodopsin. Bio-chemistry, 43, 12819-12828. doi:10.1021/bi0491191
[34] Teller, D.C., Okada, T., Behnke, C.A., Palczewski, K. and Stenkamp R.E. (2001) Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptor (GPCRs). Biochemistry, 40, 7761-7772. doi:10.1021/bi0155091
[35] Kholmurodov, Kh.T., Feldman, T.B. and Ostrovskii, M.A. (2007) Molecular dynamics of rhodopsin and free opsin: Computer simulation. Neuroscience and Behavioral Physiology, 37, 161-174. doi:10.1007/s11055-007-0164-7

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