20.500.12556/DKUM-85181 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 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. manganese superoxide dismutase polymorphism rs4880 mutation Ala16Val molecular dynamics simulations oxidative stress polimorfizmi dinamika molekul polimorfizem rs4880 mutacija Ala16Val oksidativni stres true false true MDPI AG Angleški jezik Slovenski jezik https://www.mdpi.com/journal/antioxidants © 2022 by the authors Znanstveno delo 2023-08-21 15:10:17 2023-08-21 15:10:17 2025-04-10 07:38:50 0000-00-00 00:00:00 2022 0 0 18 str. Št. 12 Letn. 11 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2022-10-20 2022-11-25 2022-11-27 543 131249155 10.3390/antiox11122348 2076-3921 The_Effect_of_the_Ala16Val_Mutation-Broz-2022.pdf The_Effect_of_the_Ala16Val_Mutation-Broz-2022.pdf 1 D846FA3D80E007D814B11A356A282C61 99244a936d77ec4d2a7e5186a85f8dba0e4b520928be26761caf129d20f53893 31e633b2-4025-11ee-a9b1-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=169958 https://www.mdpi.com/2076-3921/11/12/2348 0 3866516c-4025-11ee-a9b1-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=169959 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0