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.
Similar content being viewed by others
References
Mattson MP (2004) Nature 430:631–639
Hardy J, Selkoe DJ (2002) Science 297:353–356
McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL (1999) Ann Neurol 46:860–866
Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ (2002) Selkoe DJ 416:535–539
Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) Neurol Sci 158:47–52
Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, Cuajungco MP, Gray DN, Lim J, Moir RD, Tanzi RE (1999) Biochemistry 38:7609–7616
Cutler G, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Proc Natl Acad Sci 101:2070–2075
Curtain CC, Ali F, Volitakis I, Cherny RA, Norton RS, Beyreuther K, Barrow CJ, Masters CL, Bush AI, Barnham KJ (2001) J Biol Chem 276:20466–20473
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 18:1427–1429
Butterfield DA, Boyd-Kimball D (2005) Biochim Biophys Acta Proteins & Proteomics 1703:149–156
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) 280-13355–13363
Ciccotosto GD, Barnham KJ, Cherny RA, Masters CL, Bush AI, Curtain CC, Cappai R, Tew D (2003) Lett Pep Sci 10:413–417
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, CT
Jaguar version 6.0 Schrodinger, LLC, Portland, OR, (2005)
Pogocki D (2004) Chem Res Toxicol 17:325–329
Guilloreau L, Damian L, Coppel Y, Mazarguil H, Winterhalter M, Faller P (2006) J Biol Inorg Chem 11:1024–1038
Streltosov VA, Titmuss SJ, Epa VC, Barnham KJ, Masters CL, Varghese JN (2008) Biophys J 95:3447–3456
Drew SC, Noble CJ, Masters CL, Hanson GR, Barnham KJ (2009) J Am Chem Soc 131:1195–1207
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 H2O
Dougherty DA (1996) Science 271:163–168
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 274:37111–37116
Sanaullah, Wilson GS, Glass RS (1994) J Inorg Biochem 55:87–93
Pogocki D, Serdiuk K, Schöneich C (2003) J Phys Chem A 107:7032–7042
Huang LM, Rauk A (2004) J Phys Chem A 108:6222–6230
Bonesi SM, Manet I, Freccero M, Fagnoni M, Albini A (2006) Chemistry - A european journal 12:4844–4857
Egnaczyk GF, Greis KD, Stimson ER, Maggio JE (2001) Biochemistry 40:11706–11714
Murakami K, Irie K, Ohigashi H, Hara H, Nagao M, Shimizu T, Shirasawa T (2005) J Am Chem Soc 127:15168–15174
Murakami K, Hara H, Masuda Y, Ohigashi H, Irie K (2007) Chembiochem 8:2308–2314
Foote CS, Peters JW (1971) J Am Chem Soc 93:3795–3796
Correa PE, Riley DP (1985) J Org Chem 50:1787–1788
Prigge ST, Eipper BA, Mains RE, Amzel LM (2004) Science 304:864–867
Baciocchi E, Del Giacco T, Elisei F, Gerini MF, Guerra M, Lapi A, Liberali P (2003) J Am Chem Soc 125:16444–16454
Chu J-W, Trout BL (2004) J Am Chem Soc 126:900–908
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Haeffner, F., Barnham, K.J., Bush, A.I. et al. Generation of soluble oligomeric β-amyloid species via copper catalyzed oxidation with implications for Alzheimer’s disease: A DFT study. J Mol Model 16, 1103–1108 (2010). https://doi.org/10.1007/s00894-009-0619-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00894-009-0619-6