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Journal of Molecular Modeling

, Volume 16, Issue 6, pp 1103–1108 | Cite as

Generation of soluble oligomeric β-amyloid species via copper catalyzed oxidation with implications for Alzheimer’s disease: A DFT study

  • Fredrik Haeffner
  • Kevin J. Barnham
  • Ashley I. Bush
  • Tore BrinckEmail author
Original Paper

Abstract

A mechanism for the oxidation of a dimeric β-amyloid copper ion complex is proposed based on DFT calculations. It involves the Met35 residue, which is believed to be important in the neurotoxicity causing Alzheimer’s disease. Oxidation of Met35 is found to proceed readily with dioxygen when two Met35 residues are close to each other and the copper ion. This indicates that oxidants, such as hydrogen peroxide, are not necessary for oxidation of β-amyloid copper ion complexes. Understanding these processes could be pivotal in gaining more knowledge of this complex disease and for the development of therapeutic treatments.

Keywords

Alzheimer’s disease β-amyloid Copper ion Met35 Molecular modeling Oxidation 

References

  1. 1.
    Mattson MP (2004) Nature 430:631–639CrossRefGoogle Scholar
  2. 2.
    Hardy J, Selkoe DJ (2002) Science 297:353–356CrossRefGoogle Scholar
  3. 3.
    McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL (1999) Ann Neurol 46:860–866CrossRefGoogle Scholar
  4. 4.
    Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ (2002) Selkoe DJ 416:535–539Google Scholar
  5. 5.
    Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) Neurol Sci 158:47–52CrossRefGoogle Scholar
  6. 6.
    Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, Cuajungco MP, Gray DN, Lim J, Moir RD, Tanzi RE (1999) Biochemistry 38:7609–7616CrossRefGoogle Scholar
  7. 7.
    Cutler G, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Proc Natl Acad Sci 101:2070–2075CrossRefGoogle Scholar
  8. 8.
    Curtain CC, Ali F, Volitakis I, Cherny RA, Norton RS, Beyreuther K, Barrow CJ, Masters CL, Bush AI, Barnham KJ (2001) J Biol Chem 276:20466–20473CrossRefGoogle Scholar
  9. 9.
    Barnham KJ, Haeffner F, Ciccotosto GD, Curtain CC, Tew D, Mayros C, Beyreuther K, Carrington D, Masters CL, Cherny RA, Cappai RR, Bush AI (2004) FASEB J 18:1427–1429Google Scholar
  10. 10.
    Butterfield DA, Boyd-Kimball D (2005) Biochim Biophys Acta Proteins & Proteomics 1703:149–156CrossRefGoogle Scholar
  11. 11.
    Tickler AK, Smith DG, Ciccotosto GD, Tew DJ, Curtain CC, Carrington D, Masters CL, Bush AI, Cherny RA, Cappai R, Wade JD, Barnham KJ (2005) 280-13355–13363Google Scholar
  12. 12.
    Ciccotosto GD, Barnham KJ, Cherny RA, Masters CL, Bush AI, Curtain CC, Cappai R, Tew D (2003) Lett Pep Sci 10:413–417CrossRefGoogle Scholar
  13. 13.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Vreven T Jr, 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, Bakken V, 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, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara M, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian 03, Revision E.01. Gaussian Inc, Wallingford, CTGoogle Scholar
  14. 14.
    Jaguar version 6.0 Schrodinger, LLC, Portland, OR, (2005)Google Scholar
  15. 15.
    Pogocki D (2004) Chem Res Toxicol 17:325–329CrossRefGoogle Scholar
  16. 16.
    Guilloreau L, Damian L, Coppel Y, Mazarguil H, Winterhalter M, Faller P (2006) J Biol Inorg Chem 11:1024–1038CrossRefGoogle Scholar
  17. 17.
    Streltosov VA, Titmuss SJ, Epa VC, Barnham KJ, Masters CL, Varghese JN (2008) Biophys J 95:3447–3456CrossRefGoogle Scholar
  18. 18.
    Drew SC, Noble CJ, Masters CL, Hanson GR, Barnham KJ (2009) J Am Chem Soc 131:1195–1207CrossRefGoogle Scholar
  19. 19.
    A correction of 11.9 kcal mol−1 has been included for changing the standard state from 1 M in all species to 10−7 M in H3O+ and 55 M in H2OGoogle Scholar
  20. 20.
    Dougherty DA (1996) Science 271:163–168CrossRefGoogle Scholar
  21. 21.
    Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI (1999) J Biol Chem 274:37111–37116CrossRefGoogle Scholar
  22. 22.
    Sanaullah, Wilson GS, Glass RS (1994) J Inorg Biochem 55:87–93CrossRefGoogle Scholar
  23. 23.
    Pogocki D, Serdiuk K, Schöneich C (2003) J Phys Chem A 107:7032–7042CrossRefGoogle Scholar
  24. 24.
    Huang LM, Rauk A (2004) J Phys Chem A 108:6222–6230CrossRefGoogle Scholar
  25. 25.
    Bonesi SM, Manet I, Freccero M, Fagnoni M, Albini A (2006) Chemistry - A european journal 12:4844–4857CrossRefGoogle Scholar
  26. 26.
    Egnaczyk GF, Greis KD, Stimson ER, Maggio JE (2001) Biochemistry 40:11706–11714CrossRefGoogle Scholar
  27. 27.
    Murakami K, Irie K, Ohigashi H, Hara H, Nagao M, Shimizu T, Shirasawa T (2005) J Am Chem Soc 127:15168–15174CrossRefGoogle Scholar
  28. 28.
    Murakami K, Hara H, Masuda Y, Ohigashi H, Irie K (2007) Chembiochem 8:2308–2314CrossRefGoogle Scholar
  29. 29.
    Foote CS, Peters JW (1971) J Am Chem Soc 93:3795–3796CrossRefGoogle Scholar
  30. 30.
    Correa PE, Riley DP (1985) J Org Chem 50:1787–1788CrossRefGoogle Scholar
  31. 31.
    Prigge ST, Eipper BA, Mains RE, Amzel LM (2004) Science 304:864–867CrossRefGoogle Scholar
  32. 32.
    Baciocchi E, Del Giacco T, Elisei F, Gerini MF, Guerra M, Lapi A, Liberali P (2003) J Am Chem Soc 125:16444–16454CrossRefGoogle Scholar
  33. 33.
    Chu J-W, Trout BL (2004) J Am Chem Soc 126:900–908CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Fredrik Haeffner
    • 1
    • 2
  • Kevin J. Barnham
    • 3
  • Ashley I. Bush
    • 4
  • Tore Brinck
    • 1
    Email author
  1. 1.Physical Chemistry, Royal Institute of TechnologyStockholmSweden
  2. 2.Chemical Science and Technology Laboratory, National Institute of Standards and TechnologyGaithersburgUSA
  3. 3.Department of PathologyThe University of Melbourne, and The Mental Health Research Institute of VictoriaMelbourneAustralia
  4. 4.Laboratory for Oxidation Biology, Genetics and Aging Research Unit and Department of PsychiatryHarvard Medical SchoolBostonUSA

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