Functional and structural analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the MYB oncoproteins associated with human cancer

Abstract

MYB proteins are highly conserved DNA-binding domains (DBD) and mutations in MYB oncoproteins have been reported to cause aberrant and augmented cancer progression. Identification of MYB molecular biomarkers predictive of cancer progression can be used for improving cancer management. To address this, a biomarker discovery pipeline was employed in investigating deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in predicting damaging and potential alterations on the properties of proteins. The nsSNP of the MYB family; MYB, MYBL1, and MYBL2 was extracted from the NCBI database. Five in silico tools (PROVEAN, SIFT, PolyPhen-2, SNPs&GO and PhD-SNP) were utilized to investigate the outcomes of nsSNPs. A total of 45 nsSNPs were predicted as high-risk and damaging, and were subjected to PMut and I-Mutant 2.0 for protein stability analysis. This resulted in 32 nsSNPs with decreased stability with a DDG score lower than − 0.5, indicating damaging effect. G111S, N183S, G122S, and S178C located within the helix-turn-helix (HTH) domain were predicted to be conserved, further posttranslational modifications and 3-D protein analysis indicated these nsSNPs to shift DNA-binding specificity of the protein thus altering the protein function. Findings from this study would help in the field of pharmacogenomic and cancer therapy towards better intervention and management of cancer.

Expression pattern and clinical value of Key RNA methylation modification regulators in ischemic stroke

“…The average DDG was -0.73 kcal/mol. According to reference criteria, DDG < -0.5, indicating large decrease of protein structure stability ( Lim et al, 2021 ). In our article, ARG 215 was hydrogen binding location, results of mutation revealing the important function of this location.…”

Analyzing the Effects of Single Nucleotide Polymorphisms on hnRNPA2/B1 Protein Stability and Function: Insights for Anticancer Therapeutic Design

“…Fundamentally, functions of a protein are defined and confined by the protein primary structure (i.e., amino acid sequence) that determines its three-dimensional structure . However, a nsSNP may impair the structure and functions of a protein; for instance, Lim et al (2021) observed alteration of the DNA-binding specificities of MYB family proteins due to nsSNPs and PTMs . The results obtained from the SNP search and analyses revealed two important nsSNPs, namely, F66L and E92K, and both were predicted as a pathogenic substitution (Table ).…”

“… 32 However, a nsSNP may impair the structure and functions of a protein; for instance, Lim et al (2021) observed alteration of the DNA-binding specificities of MYB family proteins due to nsSNPs and PTMs. 33 The results obtained from the SNP search and analyses revealed two important nsSNPs, namely, F66L and E92K, and both were predicted as a pathogenic substitution ( Table 2 ). Protein’s stability is an indicator of how well a protein keeps a particular shape.…”

In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis

“…In this study, the nsSNPs of FGF4 were subjected to different bioinformatics tools to determine their structural and functional effect on the protein [ 30 ]. Damaging nsSNPs were predicted using five different tools, resulting in 27 nsSNPs as “highly damaging”.…”