Computational prediction of nsSNPs effects on bovine GSTP1: an integrated protein function and structure approach to SNPs prioritization

ALVAREZ, P.; ROGBERG-MUÑOZ A.; FALOMIR LOCKHART AH; VILLEGAS-CASTAGNASO, E.E.; CRESPI, J.; GIOVAMBATTISTA, G.

La Plata

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

Sociedad Argentina de Biofísica

The glutathione S-transferases (GSTs) superfamily protects against reactivespecies and substances, minimizing oxidative stress. Additionally, it regulates the apoptotic processes through a non-enzymatic interaction with signaling kinases. Previous studies have shown that GSTP1 haplotypes produce differences on cellular proliferation and apoptosis. Therefore, analysis of the genetic variability and of the potential impact of amino acid variants on protein structure and function by cost-effective and reliable in silico methods could enhance our understanding of GSTP1 involvement in muscle redox state and apoptosis. In particular, post mortem conversion of animal muscle into meat involves apoptosis and could be used as a model of cellular extreme oxidative stress leading to programmed cell death. In this research, bovine GSTP1 gene was resequenced and fifteen exonic SNPs were detected, some of them leading to amino acids substitution (non synonymous SNPs). The possible impact of these mutations on protein structure and function was tested by a combination of tools based onevolutionary and structural information. Next, homology modeling was performed to predict and compare the 3D protein structures of unresolved amino acid sequences. 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 GSTP1 protein using prioritization bioinformatics tools before conducting in vitro or in vivo experimental studies.