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Theoretical Chemistry Accounts

, Volume 120, Issue 4–6, pp 429–435 | Cite as

Proton catalyzed hydrolytic deamination of cytosine: a computational study

  • V. Labet
  • A. Grand
  • C. Morell
  • J. Cadet
  • L. A. ErikssonEmail author
Regular Article

Abstract

Two pathways involving proton catalyzed hydrolytic deamination of cytosine (to uracil) are investigated at the PCM-corrected B3LYP/6-311G(d,p) level of theory, in the presence of an additional catalyzing water molecule. It is concluded that the pathway involving initial protonation at nitrogen in position 3 of the ring, followed by water addition at C4 and proton transfer to the amino group, is a likely route to hydrolytic deamination. The rate determining step is the addition of water to the cytosine, with a calculated free energy barrier in aqueous solution of ΔG =140 kJ/mol. The current mechanism provides a lower barrier to deamination than previous work based on OH catalyzed reactions, and lies closer to the experimental barrier derived from rate constants (E a = 117  ±  4 kJ/mol).

Keywords

Cytosine Hydrolytic deamination B3LYP Mutation DNA 

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References

  1. 1.
    Burgur A (1983). A Guide to the Chemical Basis of Drug Design. Wiley, New York Google Scholar
  2. 2.
    Peng W and Shaw BR (1996). Biochemistry 35: 10172–10181 CrossRefGoogle Scholar
  3. 3.
    Florián J, Baumruk V and Leszczyñski J (1996). J Phys Chem 100: 5578–5589 CrossRefGoogle Scholar
  4. 4.
    Sponer J, Leszczynski J and Hobza P (1996). J Comput Chem 117: 841–850 CrossRefGoogle Scholar
  5. 5.
    Estrin DA, Paglieri L and Corongiu G (1994). J Phys Chem 98: 5653–5660 CrossRefGoogle Scholar
  6. 6.
    Scanlan MJ and Hillier IH (1984). J Am Chem Soc 106: 3737–3745 CrossRefGoogle Scholar
  7. 7.
    Chandra AK, Nguyen MT and Zeegers-Huyskens T (2000). J Mol Struct (Theochem) 519: 1–11 Google Scholar
  8. 8.
    Chandra AK, Michalska D, Wysokinsky R and Zeegers-Huyskens T (2004). J Phys Chem A 108: 9593–9600 CrossRefGoogle Scholar
  9. 9.
    Civcir PÜ (2000). J Mol Struc (Theochem) 532: 157–169 CrossRefGoogle Scholar
  10. 10.
    Gould IR, Green DVS, Young P and Hillier IH (1992). J Org Chem 57: 4434–4437 CrossRefGoogle Scholar
  11. 11.
    Morpurgo S, Bossa M and Morpurgo GO (2000). Adv Quantum Chem 36: 169–183 Google Scholar
  12. 12.
    Sambrano JR, Souza AR, Queralt JJ and Andrés J (2000). Chem Phys Lett 317: 437–443 CrossRefGoogle Scholar
  13. 13.
    Colominas C, Luque FJ and Orozco M (1996). J Am Chem Soc 118: 6811–6821 CrossRefGoogle Scholar
  14. 14.
    Fogarasi G (2002). J Phys Chem A 106: 1381–1390 CrossRefGoogle Scholar
  15. 15.
    Fogarasi G and Szalay PG (2002). Chem Phys Lett 356: 383–390 CrossRefGoogle Scholar
  16. 16.
    Person WB, Szczepaniak K, Szczesniak M, Kwiatkowski JS, Hernandez L and Czerminski R (1989). J Mol Struc (Theochem) 194: 239–258 Google Scholar
  17. 17.
    Brown RD, Godfrey PD, McNaughton D and Pierlot AP (1989). J Am Chem Soc 111: 2308–2310 CrossRefGoogle Scholar
  18. 18.
    Monajjemi M, Ghiasi R, Ketabi S, Passdar H, Mollaamin F (2004) pp 11–18Google Scholar
  19. 19.
    Monajjemi M, Ghiasi R and Abedi A (2005). Theor Inorg Chem 50: 435–441 Google Scholar
  20. 20.
    Burda J, Sponer J, Leszczynski J and Hobza P (1997). J Phys Chem B 101: 9670–9677 CrossRefGoogle Scholar
  21. 21.
    Sponer J, Burda JV, Sabat M, Leszczynski J and Hobza P (1998). J Phys Chem A 102: 5951–5957 CrossRefGoogle Scholar
  22. 22.
    Sponer JE, Miguel PJ, Rodruigez-Santiago L, Erxleben A, Krumm M, Sodupe M, Sponer J and Lippert B (2004). Angew Chem Int Ed 43: 5396–5399 CrossRefGoogle Scholar
  23. 23.
    Russo N, Toscano M and Grand A (2001). J Phys Chem B 105: 4735–4741 CrossRefGoogle Scholar
  24. 24.
    Russo N, Sicilia E, Toscano M and Grand A (2002). Int J Quantum Chem 90: 903–909 CrossRefGoogle Scholar
  25. 25.
    Russo N, Toscano M and Grand A (2001). J Am Chem Soc 123: 10272–10279 CrossRefGoogle Scholar
  26. 26.
    Russo N, Toscano M and Grand A (2003). J Mass Spectrom 38: 265–270 CrossRefGoogle Scholar
  27. 27.
    Russo N, Toscano M and Grand A (2003). J Phys Chem A 107: 11533–11538 CrossRefGoogle Scholar
  28. 28.
    Marino T, Toscano M, Russo N and Grand A (2004). Int J Quantum Chem 98: 347–354 CrossRefGoogle Scholar
  29. 29.
    Marino T, Mazzuca D, Toscano M, Russo N and Grand A (2007). Int J Quantum Chem 107: 311–317 CrossRefGoogle Scholar
  30. 30.
    Brown D and Phillips JH (1965). J Mol Biol 11: 663–671 CrossRefGoogle Scholar
  31. 31.
    Notari RE, Chin ML and Cardoni A (1970). J Pharm Sci 59: 27–32 CrossRefGoogle Scholar
  32. 32.
    Dreyfus M, Bensaude O, Dodin G and Dubois JE (1976). J Am Chem Soc 98: 6338–6349 CrossRefGoogle Scholar
  33. 33.
    Shapiro R and Klein R (1966). Biochemistry 5: 2358–2362 CrossRefGoogle Scholar
  34. 34.
    Chen H and Shaw BR (1994). Biochemistry 33: 4121–4129 CrossRefGoogle Scholar
  35. 35.
    Glaser R, Rayat S, Lewis M, Son M-S and Meyer S (1999). J Am Chem Soc 121: 6108–6119 CrossRefGoogle Scholar
  36. 36.
    Shapiro R and Klein R (1967). Biochemistry 6: 3576–3782 CrossRefGoogle Scholar
  37. 37.
    Frederico LA:, Kunkel TA and Shaw BR (1990). Biochemistry 29: 2532–2537 CrossRefGoogle Scholar
  38. 38.
    Lindahl T and Nyberg B (1974). Biochemistry 13: 3405–3410 CrossRefGoogle Scholar
  39. 39.
    Duncan BK and Miller JH (1980). Nature 287: 560–561 CrossRefGoogle Scholar
  40. 40.
    Almatarneh MH, Flinn CG, Poirier RA and Sokalski WA (2006). J Phys Chem A 110: 8227–8234 CrossRefGoogle Scholar
  41. 41.
    Yao L, Li Y, Wu Y, Liu A and Yan H (2005). Biochemistry 44: 5940–5947 CrossRefGoogle Scholar
  42. 42.
    Becke AD (1993). J Chem Phys 98: 5648–5652 CrossRefGoogle Scholar
  43. 43.
    Lee C, Yang W and Parr RG (1988). Phys Rev B 37: 785–789 CrossRefGoogle Scholar
  44. 44.
    McLean AD and Chandler GS (1980). J Chem Phys 72: 5639 CrossRefGoogle Scholar
  45. 45.
    Krishnan R, Binkley JS, Seeger R and Pople JA (1980). J Chem Phys 72: 650 CrossRefGoogle Scholar
  46. 46.
    Frisch MJ, Pople JA and Binkley JS (1984). J Chem Phys 80: 3265 CrossRefGoogle Scholar
  47. 47.
    Cancès MT, Mennucci B and Tomasi J (1997). J Chem Phys 107: 3032–3041 CrossRefGoogle Scholar
  48. 48.
    Mennucci B and Tomasi J (1997). J Chem Phys 106: 5151–5158 CrossRefGoogle Scholar
  49. 49.
    Cossi M, Scalmani G, Rega N and Barone V (2002). J Chem Phys 117: 43–54 CrossRefGoogle Scholar
  50. 50.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA Jr, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskortz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chem W, Wong MW, Gonzalez C, Pople JA. Gaussian 03, Revision C.02, Gaussian: Wallingford, 2004Google Scholar
  51. 51.
    Llano J and Eriksson LA (2002). J Chem Phys 117: 10193–10206 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • V. Labet
    • 1
  • A. Grand
    • 1
  • C. Morell
    • 1
  • J. Cadet
    • 1
  • L. A. Eriksson
    • 2
    Email author
  1. 1.Laboratoire “Lésions des Acides Nucléiques”DRFMC/SCIB, UMR-E 3 (CEA/UJF), CEA-GrenobleGrenoble Cedex 9France
  2. 2.Department of Natural Sciences and Örebro Life Science CenterÖrebro UniversityÖrebroSweden

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