Citation: XU Zhao-Ying, ZHAO Li-Ling, CAO Zan-Xia, WANG Ji-Hua. Effects of the Residue Mutations on the Segment of P53-DNA Binding Region Based on Molecular Dynamics Simulation[J]. Acta Physico-Chimica Sinica, ;2012, 28(07): 1665-1675. doi: 10.3866/PKU.WHXB201204182 shu

Effects of the Residue Mutations on the Segment of P53-DNA Binding Region Based on Molecular Dynamics Simulation

XU Zhao-Ying ^1,3 ,
ZHAO Li-Ling ^1,2 ,
CAO Zan-Xia ^1,2 ,
WANG Ji-Hua ^1,2,

1.
1. Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics (Dezhou University), Dezhou 253023, Shandong Province, P. R. China;
2. Department of Physics, Dezhou University, Dezhou 253023, Shandong Province, P. R. China;
3. College of Physics and Electronics, Shandong Normal University, Jinan 250014, P. R. China

Received Date: 10 January 2012
Available Online: 18 April 2012
Fund Project: 国家自然科学基金(30970561, 31000324) (30970561, 31000324)山东省自然科学基金(2009ZRA14027, 2009ZRA14028)资助项目 (2009ZRA14027, 2009ZRA14028)

The structural characteristics of the peptide segment of the P53-DNA binding domain (from residue 230 to 258) were studied using molecular dynamics simulations with different mutations, including R249S, R248W, and G245S. Four independent simulations, including the wild-type segment wtP53, onepoint mutation segment P53-R249S, two-point mutation segment P53-R249S/R248W, and three-point mutation segment P53-R249S/R248W/G245S, were performed using the GROMACS software package and GROMOS 43A1 force field. Each simulation was run for 500 ns. The results indicated that mutation R249S affected the formation of the secondary structure for some residues, but had little impact on the mode of the ternary structure and made the segment more stable than the wild-type segment. In contrast, the R249S/R248W mutation strengthened the effect of R249S on the segment and induced a significant change in the ternary structure, with the structure of the two-point mutation segment R249S/R248W existing as a double-turn motif and becoming more stable. Moreover, the G245S mutation had the opposite effect on the segment, decreasing or eliminating entirely the effects caused by the R249S/R248W mutation on the segment. This study provided important understanding of the molecular mechanism of tumorigenesis and the design of a new drug.
- P53 protein,
- Residue mutation,
- Structural change,
- Molecular dynamics simulation,
- Structure heterogeneity
1. [1]
  
  (1) Attardi, L. D.; Donehower, L. A. Mutat. Res. 2005, 576 (1-2),4. doi: 10.1016/j.mrfmmm.2004.08.022
2. [2]
  (2) Fazeli, A.; Steen, R. G.; Dickinson, S. L.; Bautista, D.; Dietrich,W. F.; Bronson, R. T.; Bresalier, R. S.; Lander, E. S.; Costa, J.;Weinberg, R. A. Proc. Natl. Acad. Sci. U. S. A. 1997, 94 (19),10199. doi: 10.1073/pnas.94.19.10199
3. [3]
  (3) Wang,W.; El-Deiry,W. S. Curr. Opin. Oncol. 2008, 20 (1), 90.doi: 10.1097/CCO.0b013e3282f31d6f
4. [4]
  (4) Barlev, N. A.; Sayan, B. S.; Candi, E.; Okorokov, A. L. Cell Death Differ. 2010, 17 (2), 373. doi: 10.1038/cdd.2009.73
5. [5]
  (5) Botcheva, K.; McCorkle, S. R.; McCombie,W. R.; Dunn, J. J.;Anderson, C.W. Cell Cycle 2011, 10 (24), 4237. doi: 10.4161/cc.10.24.18383
6. [6]
  (6) Romer, L.; Klein, C.; Dehner, A.; Kessler, H.; Buchner, J.Angew. Chem. Int. Edit. Engl. 2006, 45 (39), 6440. doi: 10.1002/anie.200600611
7. [7]
  (7) Cho, Y.; rina, S.; Jeffrey, P. D.; Pavletich, N. P. Science 1994,265 (5170), 346. doi: 10.1126/science.8023157
8. [8]
  (8) Joerger, A. C.; Fersht, A. R. Annu. Rev. Biochem. 2008, 77,557. doi: 10.1146/annurev.biochem.77.060806.091238
9. [9]
  (9) Rustandi, R. R.; Baldisseri, D. M.;Weber, D. J. Nat. Struct. Biol. 2000, 7 (7), 570. doi: 10.1038/76797
10. [10]
  (10) Tidow, H.; Melero, R.; Mylonas, E.; Freund, S. M.; Grossmann,J. G.; Carazo, J. M.; Svergun, D. I.; Valle, M.; Fersht, A. R.Proc. Natl. Acad. Sci. U. S. A. 2007, 104 (30), 12324. doi: 10.1073/pnas.0705069104
11. [11]
  (11) Dawson, R.; Muller, L.; Dehner, A.; Klein, C.; Kessler, H.;Buchner, J. J. Mol. Biol. 2003, 332 (5), 1131. doi: 10.1016/j.jmb.2003.08.008
12. [12]
  (12) Terakawa, T.; Takada, S. Biophys. J. 2011, 101 (6), 1450. doi: 10.1016/j.bpj.2011.08.003
13. [13]
  (13) Pavletich, N. P.; Chambers, K. A.; Pabo, C. O. Genes Dev. 1993,7 (12B), 2556. doi: 10.1101/gad.7.12b.2556
14. [14]
  (14) Weinberg, R. L.; Veprintsev, D. B.; Fersht, A. R. J. Mol. Biol.2004, 341 (5), 1145. doi: 10.1016/j.jmb.2004.06.071
15. [15]
  (15) Bullock, A. N.; Fersht, A. R. Nat. Rev. Cancer 2001, 1 (1),68. doi: 10.1038/35094077
16. [16]
  (16) Petitjean, A.; Achatz, M. I.; Borresen-Dale, A. L.; Hainaut, P.;Olivier, M. Oncogene 2007, 26 (15), 2157. doi: 10.1038/sj.onc.1210302
17. [17]
  (17) Soussi, T. Adv. Cancer Res. 2011, 110, 107. doi: 10.1016/B978-0-12-386469-7.00005-0
18. [18]
  (18) Ang, H. C.; Joerger, A. C.; Mayer, S.; Fersht, A. R. J. Biol. Chem. 2006, 281 (31), 21934. doi: 10.1074/jbc.M604209200
19. [19]
  (19) Tidow, H.; Veprintsev, D. B.; Freund, S. M.; Fersht, A. R.J. Biol. Chem. 2006, 281 (43), 32526. doi: 10.1074/jbc.M604725200
20. [20]
  (20) Szymanska, K.; Chen, J. G.; Cui, Y.; ng, Y. Y.; Turner, P. C.;Villar, S.;Wild, C. P.; Parkin, D. M.; Hainaut, P. Cancer Epidemiol. Biomarkers Prev. 2009, 18 (5), 1638. doi: 10.1158/1055-9965.EPI-08-1102
21. [21]
  (21) uas, D.; Shi, H.; Hainaut, P. Cancer Lett. 2009, 286 (1), 29.doi: 10.1016/j.canlet.2009.02.057
22. [22]
  (22) Friedler, A.; DeDecker, B. S.; Freund, S. M.; Blair, C.; Rudiger,S.; Fersht, A. R. J. Mol. Biol. 2004, 336 (1), 187. doi: 10.1016/j.jmb.2003.12.005
23. [23]
  (23) Suad, O.; Rozenberg, H.; Brosh, R.; Diskin-Posner, Y.; Kessler,N.; Shimon, L. J.; Frolow, F.; Liran, A.; Rotter, V.; Shakked, Z.J. Mol. Biol. 2009, 385 (1), 249.
24. [24]
  (24) Rauf, S. M.; Ismael, M.; Sahu, K. K.; Suzuki, A.; Koyama, M.;Tsuboi, H.; Hatakeyama, N.; Endou, A.; Takaba, H.; Del Carpio,C. A.; Kubo, M.; Miyamoto, A. Comput. Biol. Med. 2010, 40 (5), 498. doi: 10.1016/j.compbiomed.2010.03.004
25. [25]
  (25) Zhao, J.; Guo, Z. K. Journal of Northwest Agriculture and Forestry University (Nat. Sci. Ed.) 2008, 36 (10), 186.[赵晶, 郭泽坤. 西北农林科技大学学报(自然科学版), 2008,36 (10), 186.]
26. [26]
  (26) Wang, R.; ng, Z. H.; Jiang, L. X.; Sun, D. J.; Jiao, A. H.;Chen, J.; Zhang, L. M. China Oncology 2010, 21 (3), 177.
27. [27]
  (27) Barakat, K.; Issack, B. B.; Stepanova, M.; Tuszynski, J. PLos One 2011, 6 (11), e27651.
28. [28]
  (28) Cao, Z.; Liu, L.;Wu, P.;Wang, J. Acta Biochim. Biophys. Sin.2011, 43 (3), 172.
29. [29]
  (29) Shaw, D. E.; Maragakis, P.; Lindorff-Larsen, K.; Piana, S.; Dror,R. O.; Eastwood, M. P.; Bank, J. A.; Jumper, J. M.; Salmon, J.K.; Shan, Y.;Wriggers,W. Science 2010, 330 (6), 341. doi: 10.1126/science.1187409
30. [30]
  (30) Guex, N.; Peitsch, M. C. Electrophoresis 1997, 18 (15), 2714.doi: 10.1002/elps.1150181505
31. [31]
  (31) Guex, N.; Peitsch, M. C.; Schwede, T. Electrophoresis 2009, 30 (Suppl 1), S162.
32. [32]
  (32) Kutzner, C.; Czub, J.; Grubmuller, H. J. Chem. Theory Comput.2011, 7 (5), 1381. doi: 10.1021/ct100666v
33. [33]
  (33) van Der Spoel, D.; Lindahl, E.; Hess, B.; Groenhof, G.; Mark,A. E.; Berendsen, H. J. J. Comput. Chem. 2005, 26 (16),1701. doi: 10.1002/jcc.20291
34. [34]
  (34) Lin, Z.; van Gunsteren,W. F.; Liu, H. J. Comput. Chem. 2011,32 (10), 2290. doi: 10.1002/jcc.21818
35. [35]
  (35) Stocker, U.; van Gunsteren,W. F. Proteins 2000, 40 (1),145. doi: 10.1002/(SICI)1097-0134(20000701)40:1<145:AIDPROT160>3.0.CO;2-Y
36. [36]
  (36) Berlinski, E.;Wojcikowski, C.; Horoszek-Maziarz, S.; Krupa-Wojciechowska, B. Endokrynol Pol. 1981, 32 (2), 117.
37. [37]
  (37) Chatterjee, S.; Debenedetti, P. G.; Stillinger, F. H.; Lynden-Bell,R. M. J. Chem. Phys. 2008, 128 (12), 124511. doi: 10.1063/1.2841127
38. [38]
  (38) Berendsen, H. J. C.; Postma, J. P. M.; Gunsteren,W. F. V.J. Chem. Phys. 1984, 81 (8), 3684. doi: 10.1063/1.448118
39. [39]
  (39) Frishman, D.; Ar s, P. Proteins 1995, 23 (4), 566. doi: 10.1002/prot.340230412
40. [40]
  (40) Hu, H.; Elstner, M.; Hermans, J. Proteins 2003, 50 (3), 1131.
41. [41]
  (41) Nikolova, P. V.;Wong, K. B.; DeDecker, B.; Henckel, J.; Fersht,A. R. EMBO J. 2000, 19 (3), 370. doi: 10.1093/emboj/19.3.370
42. [42]
  (42) Wong, K. B.; DeDecker, B. S.; Freund, S. M.; Proctor, M. R.;Bycroft, M.; Fersht, A. R. Proc. Natl. Acad. Sci. U. S. A. 1999,96 (15), 8438. doi: 10.1073/pnas.96.15.8438
43. [43]
  (43) Joerger, A. C.; Ang, H. C.; Veprintsev, D. B.; Blair, C. M.;Fersht, A. R. J. Biol. Chem. 2005, 280 (16), 16030. doi: 10.1074/jbc.M500179200
44. [44]
  (44) Francis, C. J.; Lindorff-Larsen, K.; Best, R. B.; Vendruscolo, M.Proteins 2006, 65 (1), 145. doi: 10.1002/prot.21077
45. [45]
  (45) Cao, Z.; Liu, L.;Wang, J. J. Biomol. Struct. Dyn. 2010, 28 (3),343.
46. [46]
  (46) Qiao, X.; Chen, Y.W. Int. J. Biomed. Imaging 2011, 2011,601672.
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