The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence.
manganese superoxide dismutase
molecular dynamics simulations
mutation Ala16Val
oxidative stress
polymorphism rs4880
Journal
Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981
Informations de publication
Date de publication:
27 Nov 2022
27 Nov 2022
Historique:
received:
20
10
2022
revised:
16
11
2022
accepted:
25
11
2022
entrez:
23
12
2022
pubmed:
24
12
2022
medline:
24
12
2022
Statut:
epublish
Résumé
Manganese Superoxide Dismutase (MnSOD) represents a mitochondrial protein that scavenges reactive oxygen species (ROS) responsible for oxidative stress. A known single nucleotide polymorphism (SNP) rs4880 on the SOD2 gene, causing a mutation from alanine to valine (Ala16Val) in the primary structure of immature MnSOD, has been associated with several types of cancer and other autoimmune diseases. However, no conclusive correlation has been established yet. This study aims to determine the effect of the alanine to valine mutation on the secondary structure of the MnSOD mitochondrial targeting sequence (MTS). A model for each variant of the MTS was prepared and extensively simulated with molecular dynamics simulations using the CHARMM36m force field. The results indicate that the alanine variant of the MTS preserves a uniform α-helical secondary structure favorable for the protein transport into mitochondria, whereas the valine variant quickly breaks down its α-helix. Thus, the alanine MTS represents the more active MnSOD variant, the benefits of which have yet to be determined experimentally.
Identifiants
pubmed: 36552556
pii: antiox11122348
doi: 10.3390/antiox11122348
pmc: PMC9774195
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Slovenian Research Agency
ID : P2-0046
Organisme : Slovenian Research Agency
ID : J1-2471
Organisme : Ministry of Education, Science and Sport
ID : OP20.04342
Organisme : Ministry of Education, Science and Sport
ID : C3330-19-952021
Organisme : Slovenian Research Agency
ID : L2-3175
Organisme : Slovenian Research Agency
ID : P1-0403
Références
EMBO J. 1986 Jun;5(6):1327-34
pubmed: 3015598
Nat Rev Mol Cell Biol. 2001 May;2(5):339-49
pubmed: 11331908
Toxicol Lett. 2002 Mar 28;129(3):255-62
pubmed: 11888709
Nitric Oxide. 2006 Mar;14(2):109-21
pubmed: 16352449
J Struct Biol. 2017 Jul;199(1):68-75
pubmed: 28461152
Cell. 1992 Oct 2;71(1):107-18
pubmed: 1394426
Biochem J. 1989 Oct 15;263(2):539-45
pubmed: 2556998
Clin Exp Allergy. 2010 Mar;40(3):370-80
pubmed: 19968654
Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):1089-97
pubmed: 20233853
Biochim Biophys Acta. 1989 Jan 19;994(1):30-6
pubmed: 2462451
Biochemistry (Mosc). 2005 Feb;70(2):200-14
pubmed: 15807660
EMBO J. 1986 Jun;5(6):1335-42
pubmed: 3015599
J Biol Chem. 1995 May 19;270(20):11727-30
pubmed: 7744816
Mutat Res. 2006 Jan 29;593(1-2):108-15
pubmed: 16084535
Protein Sci. 1994 May;3(5):843-52
pubmed: 8061613
World Allergy Organ J. 2011 Oct;4(10):151-8
pubmed: 23268432
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
Antioxid Redox Signal. 2011 Sep 15;15(6):1583-606
pubmed: 21473702
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2195-9
pubmed: 1549581
J Mol Biol. 1993 Dec 5;234(3):779-815
pubmed: 8254673
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Proteins. 2010 Nov 15;78(15):3096-103
pubmed: 20635420
Bioinformatics. 2000 Apr;16(4):404-5
pubmed: 10869041
Proteins. 1994 May;19(1):14-23
pubmed: 8066082
Biochemistry. 1974 Jan 15;13(2):222-45
pubmed: 4358940
J Med Biochem. 2017 Oct 28;36(4):341-348
pubmed: 30581331
Cell. 1988 Jun 3;53(5):795-806
pubmed: 2967109
Pharmacogenetics. 2003 Mar;13(3):145-57
pubmed: 12618592
J Cell Biol. 1994 Aug;126(4):1079-88
pubmed: 8051207
Exp Neurol. 2016 Mar;277:58-67
pubmed: 26626971
J Am Chem Soc. 2010 Sep 15;132(36):12525-7
pubmed: 20726524
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
Physiol Rev. 1979 Jul;59(3):527-605
pubmed: 37532
Nat Methods. 2015 Jan;12(1):7-8
pubmed: 25549265
Carcinogenesis. 2008 May;29(5):964-70
pubmed: 18296681
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W500-2
pubmed: 15215436
Proteins. 2001 Feb 15;42(3):399-413
pubmed: 11151011
Biochim Biophys Acta. 1999 May 5;1411(2-3):378-84
pubmed: 10320670
Biochem Biophys Res Commun. 1996 Sep 13;226(2):561-5
pubmed: 8806673
PLoS One. 2013 Jun 13;8(6):e65558
pubmed: 23785434
Nucleic Acids Res. 2017 Jul 3;45(W1):W365-W373
pubmed: 28521030
Nucleic Acids Res. 2016 Jul 8;44(W1):W449-54
pubmed: 27131374
J Chem Phys. 2020 Jul 28;153(4):044130
pubmed: 32752662
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5317-20
pubmed: 2052608
Nature. 1990 Mar 15;344(6263):268-70
pubmed: 2314462
Science. 1990 Nov 2;250(4981):669-73
pubmed: 2237416
Cancer Genet Cytogenet. 2009 Feb;189(1):1-4
pubmed: 19167605
Neuro Oncol. 2008 Oct;10(5):709-15
pubmed: 18682580
J Biol Chem. 1987 Nov 15;262(32):15605-9
pubmed: 3680214
J Comput Chem. 2009 Jul 30;30(10):1545-614
pubmed: 19444816
Biopolymers. 1993 Jun;33(6):971-84
pubmed: 8318669
Front Oncol. 2017 Mar 15;7:41
pubmed: 28361035
Biochem J. 2004 Sep 1;382(Pt 2):511-7
pubmed: 15175007
Curr Med Chem. 2018;25(33):4084-4101
pubmed: 28699501
Biophys J. 1967 Mar;7(2):121-35
pubmed: 6048867
Nature. 2015 Nov 12;527(7577):186-91
pubmed: 26466563
Pharmacogenetics. 2003 Mar;13(3):129-30
pubmed: 12618590
Fold Des. 1998;3(2):119-26
pubmed: 9565756
Oxid Med Cell Longev. 2013;2013:956792
pubmed: 23738047
Int J Cancer. 2007 Jun 15;120(12):2739-43
pubmed: 17290392
Biopolymers. 1987 Aug;26(8):1273-86
pubmed: 3663860
J Med Genet. 2004 Dec;41(12):946-50
pubmed: 15591282
DNA Cell Biol. 1994 Nov;13(11):1127-36
pubmed: 7702755
Structure. 2001 Jul 3;9(7):615-25
pubmed: 11470436
Structure. 1999 Mar 15;7(3):R55-60
pubmed: 10368306
J Clin Invest. 1992 Mar;89(3):1006-13
pubmed: 1311714
Cancer Res. 1999 Feb 1;59(3):602-6
pubmed: 9973207
J Biol Chem. 1973 May 25;248(10):3582-92
pubmed: 4702877
J Leukoc Biol. 1999 Mar;65(3):337-40
pubmed: 10080536
J Biol Chem. 2004 Apr 9;279(15):14473-6
pubmed: 14973134
Am J Transl Res. 2015 Feb 15;7(2):401-10
pubmed: 25901207
Amino Acids. 2003 Dec;25(3-4):295-311
pubmed: 14661092
Pharmacogenet Genomics. 2005 May;15(5):311-9
pubmed: 15864132
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4471-3
pubmed: 8633092
Annu Rev Biochem. 1995;64:97-112
pubmed: 7574505
Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1005-28
pubmed: 11076791
Clin Cancer Res. 2009 Jun 15;15(12):4165-73
pubmed: 19509150
Pharmacogenet Genomics. 2006 Apr;16(4):279-86
pubmed: 16538174
Science. 1990 Nov 2;250(4981):646-51
pubmed: 2237415
J Chem Theory Comput. 2019 Jan 8;15(1):7-12
pubmed: 30562013
Biochemistry. 1991 Jun 18;30(24):6059-70
pubmed: 2043644