Cargando…

The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Broz, Matic, Furlan, Veronika, Lešnik, Samo, Jukič, Marko, Bren, Urban
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774195/
https://www.ncbi.nlm.nih.gov/pubmed/36552556
http://dx.doi.org/10.3390/antiox11122348
_version_ 1784855349866528768
author Broz, Matic
Furlan, Veronika
Lešnik, Samo
Jukič, Marko
Bren, Urban
author_facet Broz, Matic
Furlan, Veronika
Lešnik, Samo
Jukič, Marko
Bren, Urban
author_sort Broz, Matic
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9774195
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97741952022-12-23 The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence Broz, Matic Furlan, Veronika Lešnik, Samo Jukič, Marko Bren, Urban Antioxidants (Basel) Article 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. MDPI 2022-11-27 /pmc/articles/PMC9774195/ /pubmed/36552556 http://dx.doi.org/10.3390/antiox11122348 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Broz, Matic
Furlan, Veronika
Lešnik, Samo
Jukič, Marko
Bren, Urban
The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence
title The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence
title_full The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence
title_fullStr The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence
title_full_unstemmed The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence
title_short The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence
title_sort effect of the ala16val mutation on the secondary structure of the manganese superoxide dismutase mitochondrial targeting sequence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774195/
https://www.ncbi.nlm.nih.gov/pubmed/36552556
http://dx.doi.org/10.3390/antiox11122348
work_keys_str_mv AT brozmatic theeffectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT furlanveronika theeffectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT lesniksamo theeffectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT jukicmarko theeffectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT brenurban theeffectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT brozmatic effectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT furlanveronika effectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT lesniksamo effectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT jukicmarko effectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence
AT brenurban effectoftheala16valmutationonthesecondarystructureofthemanganesesuperoxidedismutasemitochondrialtargetingsequence