COMPUTATIONAL PREDICTION OF nsSNPs EFFECTS ON BOVINE GSTP1: AN INTEGRATED PROTEIN FUNCTION AND STRUCTURE APPROACH TO SNPs PRIORITIZATION

FALOMIR LOCKHART, AGUSTIN; CRESPI, JULIAN A.; ALVAREZ, PAULO; VILLEGAS CASTAGNASSO E E; GIOVAMBATTISTA GUILLERMO; A. ROGBERG-MUÑOZ

La Plata

Congreso; XLVII Reunión Anual Sociedad Argentina de Biofisica; 2019

Sociedad Argentina de Biofisica

The glutathione S-transferases (GSTs) superfamily protects against reactivespecies and substances, minimizing oxidative stress. Additionally, it regulates theapoptotic processes through a non-enzymatic interaction with signaling kinases.Previous studies have shown that GSTP1 haplotypes produce differences oncellular proliferation and apoptosis. Therefore, analysis of the genetic variabilityand of the potential impact of amino acid variants on protein structure andfunction by cost-effective and reliable in silico methods could enhance ourunderstanding of GSTP1 involvement in muscle redox state and apoptosis. Inparticular, post mortem conversion of animal muscle into meat involves apoptosisand could be used as a model of cellular extreme oxidative stress leading toprogrammed cell death. In this research, bovine GSTP1 gene was resequenced andfifteen exonic SNPs were detected, some of them leading to amino acidssubstitution (non synonymous SNPs). The possible impact of these mutations onprotein structure and function was tested by a combination of tools based onevolutionary and structural information. Next, homology modeling was performedto predict and compare the 3D protein structures of unresolved amino acidsequences. Our results were consistent, suggesting that substitutions C15W,C48G, Q65H and L70Q may impact on GSTP1 structure and function. Moreover,haplotype analysis enabled the prioritization of three structures for furtheranalysis. This is one of the first attempts to study residue variants in bovine GSTP1protein using prioritization bioinformatics tools before conducting in vitro or in vivoexperimental studies.