Abstract
Cu–Zn superoxide dismutase 1 (SOD1) is a highly conserved bimetallic protein enzyme, used for the scavenging the superoxide radicals (O2 −) produced due to aerobic metabolism in the mitochondrial respiratory chain. Over 100 mutations have been identified and found to be in the homodimeric structure of SOD1. The enzyme has to be maintained in its dimeric state for the structural stability and enzymatic activity. From our investigation, we found that the mutations apart from the dimer interface residues are found to affect the dimer stability of protein and hence enhancing the aggregation and misfolding tendency of mutated protein. The homodimeric state of SOD1 is found to be held together by the non-covalent interactions. The molecular dynamics simulation has been used to study the hydrogen bond interactions between the dimer interface residues of the monomers in native and mutated forms of SOD1 in apo- and holo-states. The results obtained by this analysis reveal the fact that the loss of hydrogen bond interactions between the monomers of the dimer is responsible for the reduced stability of the apo- and holo-mutant forms of SOD1. The conformers with dimer interface residues in native and mutated protein obtained by the molecular dynamics simulation is subjected to quantum mechanical study using M052X/6-31G(d) level of theory. The charge transfer between N–H···O interactions in the dimer interface residues were studied. The weak interaction between the monomers of the dimer accounts for the reduced dimerization and enhanced deformation energy in the mutated SOD1 protein.
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Brown RH Jr (1995) Cell 80:687–692
Lilienfeld DE, Perl DP (1993) Neuroepidemiology 12:218–228
Sorenson EJ, Stalker AP, Kurland LT, Windebank AJ (2002) Neurology 59:280–282
Roth-Kauffman M, Niebauer J (2012) Clin Rev 22:15–21
Hough MA, Grossmann JG, Antonyuk SV, Strange RW, Doucette PA, Rodriguez JA, Whitson LJ, Hart PJ, Hayward LJ, Valentine JS, Hasnain SS (2004) Proc Natl Acad Sci USA 101:5976–5981
Das A, Plotkin SS (2013) J Mol Biol 425:850–874
Ray SS, Nowak RJ, Strokovich K, Brown RH Jr, Walz T, Lansbury PT Jr (2004) Biochemistry 43:4899–4905
Bond JM, Bannister JV, Bannnister WH (1991) Free Radic Res Commun 12–3:545–551
Goodsell DS, Olson AJ (2000) Annu Rev Biophys Biomol Struct 29:105–153
Kim J, Lee H, Lee JH, Kwon DY, Genovesio A, Fenistein D, Oqier A, Brondani V, Grailhe R (2014) J Biol Chem 289:15094–15103
Muneeswaran G, Kartheeswaran S, Muthukumar K, Dharmaraj CD, Karunakaran C (2014) Biophys Chem 185:70–78
Strange RW, Antonyuk S, Hough MA, Doucette PA, Rodriguez JA, Hart PJ, Hayward LJ, Valentine JS, Hasnain SS (2003) J Mol Biol 328:877–891
Parge HE, Hallewell RA, Tainer JA (1992) Proc Natl Acad Sci USA 89:6109–6113
Galaleldeen A, Strange RW, Whitson LJ, Antonyuk SV, Narayana N, Taylor AB, Schuermann JP, Holloway SP, Hasnain SS, Hart PJ (2009) Arch Biochem Biophys 492:40–47
DiDonato M, Craig L, Huff ME, Thayer MM, Cardoso RM, Kassmann CJ, Lo TP, Bruns CK, Powers ET, Kelly JW, Getzoff ED, Tainer JA (2003) J Mol Biol 332:601–615
Bernstein FC, Koetzle TF, Williams GJ, Meyer EF Jr, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M (1977) J Mol Biol 112:535–542
Ratovitski T, Corson LB, Strain J, Wong P, Cleveland DW, Culotta VC, Borchelt DR (1999) Hum Mol Genet 8:1451–1460
Byström R (2009) SOD1’s law: an investigation of ALS provoking properties on SOD1. Department of Chemistry, Umea University, Sweden
Reed AE, Curtiss LA, Weinhold F (1988) Chem Rev 88:899–926
Bader RFW (1990) Atoms in molecules - a quantum theory. Oxford University Press, Oxford
Zhao Y, Schultz NE, Truhlar DG (2006) J Chem Theory Comput 2:364–382
Zhao Y, Truhlar DG (2007) J Chem Theory Comput 3:289–300
Hehre WJ, Random L, Schleyer PvR, Pople JA (1986) Ab initio molecular orbital theory, 1st edn, vol 7. Wiley, New York, pp 1–379
Jurecka P, Sponer J, Cerny J, Hobza P (2006) Phys Chem Chem Phys 8:1985–1993
Fandin˜o RG, Castedo L, Granja JR, Va´zquez SA (2010) J Phys Chem B 114:4973–4983
Kim C, Kim SJ, Lee Y, Kim Y (2000) Bull Korean Chem Soc 21:510–514
Boys SF, Bernardi F (1970) Mol Phys 19:5–53
Gaussian 09, Frisch Æ, Clemente FR, Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam MJ, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian, Inc., Wallingford, CT
Kaminski GA, Friensner RA, Tirado-Rives J, Jorgensen WL (2001) J Phys Chem B 105:6474–6487
Ponder JW, Case DA (2003) Adv Protein Chem 66:27–85
Shrivastava IH, Sansom MS (2000) Biophys J 78:557–570
Berendsen HJC, Postma JPM, van Gunsteren WF, Herman J (1981) Intermol Forces 14:331–342
Moore PB, Lopez CF, Klein ML (2001) Biophys J 81:2484–2494
Miyamoto S, Kollman PA (1992) J Comput Chem 13:952–962
Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) J Chem Phys 103:8577–8594
Darden T, York D, Pedersen L (1993) J Chem Phys 98:10089–10092
Cheatham TE, Miller JL, Fox T, Darden TA, Kollman PA (1995) JAm ChemSoc 117:4193–4194
Khare SD, Caplow M, Dokholyan NV (2006) Amyloid 13:226–235
Marytyna GJ, Tobia DJ, Klein M (1994) J Chem Phys 101:4177–4189
Van der Spoel D, Lindahl E, Hess B, Van Buuren AR, Apol E, Meulenhoff PJ, Tieleman D P, Sijbers ALTM, Feenstra KA, Van Drunen R, Berendsen HJC (2010) Gromacs user manual version 4.5.4. http://www.gromacs.org
Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) J Chem Phys 81:3684–3690
Lindberg MJ, Normark J, Holmgren A, Oliveberg M (2004) Proc Natl Acad Sci USA 101:15893–15898
Anderson PM, Sim KB, Xin WW, Kiely R, O’Neil G, Ravits J, Pioro E, Harati Y, Brower RD, Levine JS, Heinicke HU, Seltzer W, Boss M, Brown RH Jr (2003) Amyotrop Lateral Scler Other Motor Neuron Disord 4:62–73
Lindberg MJ, Tibell L, Oliveberg M (2002) Proc Natl Acad Sci USA 99:16607–16612
Lindberg MJ, Bystrom R, Boknas N, Anderson PM, Oliveberg M (2005) Proc Natl Acad Sci USA 102:9754–9759
Qualls DA, Prudencio M, Roberts BLT, Crosby K, Brown H, Borchelt DR (2013) Mol Neurodegener 8:1–15
Kolandaivel P, Nirmala V (2004) J Mol Struct 694:33–38
Yuan XX, Wang YF, Wang X, Chen W, Fossey JS, Wong NB (2010) Chem Cent J 4:1–15
Doucette PA, Whitson LJ, Cao X, Schirf V, Demeler B, Valentine JS, Hansen JC, Hart PJ (2004) J Biol Chem 279:54558–54566
Zhang G, Li X, Li Y, Chen D (2013) Mol Phys 111:3276–3282
Zhang G, Xiwen L, Yan L, Chen D (2013) Mol Phys 111:3276–3282
He JY, Long ZW, Zhang JS (2011) J Struct Chem 52:1057–1062
Holm L, Sander C (1993) J Mol Biol 233:123–138
Guardia E, Marti J, Tarres LG, Laria D (2005) J Mol Liq 117:63–67
Danielsson J, Awad W, Saraboji K, Kurnik M, Lang L, Leinartaite L, Marklund SL, Logan DT, Oliveberg M (2013) Proc Natl Acad Sci USA 110:3829–3834
Shaw BF, Durazo A, Nersissian AM, Whitelegge JP, Faull KF, Valentine JS (2006) J Biol Chem 281:18167–18176
Byström R, Anderson PM, Gröbner G, Oliveberg M (2010) J Biol Chem 285:19544–19552
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The authors express their sincere thanks to HPCF Centre (High Performance Computing Facility) of DST Government of India at Hyderabad for allowing us to use the facility, where most of the calculations have been performed.
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Keerthana, S.P., Kolandaivel, P. Interaction between dimer interface residues of native and mutated SOD1 protein: a theoretical study. J Biol Inorg Chem 20, 509–522 (2015). https://doi.org/10.1007/s00775-014-1235-1
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DOI: https://doi.org/10.1007/s00775-014-1235-1