Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
ISSN: 0974-276X
This study endeavors to evaluate the potential pathogenic or benign consequences of the Liver Kinase B1 (LKB1) protein mutation, Mitogen Activated Protein Kinase p38alpha (D176A), which is categorized as a Variant of Unknown Significance (VUS). LKB1 serves as a widely recognized tumor suppressor protein with multifaceted involvement in cellular processes such as metabolism regulation and apoptosis induction. It forms a heterotrimeric complex that becomes activated through interaction with STe20-Related Adaptor (STRAD) and Mouse protein 25 (MO25). Peutz-Jeghers syndrome, an autosomal dominant hereditary disorder, is associated with mutations in the LKB1 gene. Existing evidence suggests a high likelihood of deleterious effects attributed to the amino acid substitution D176A, as inferred from the outcomes of nine out of ten predictive models. The conservation analysis conducted through the Conserved Domain Database (CDD) and aminode reveals notable preservation of the aspartate residue at position 176 across many diverse species. Despite the absence of statistically significant differences in the Root-Mean-Square Deviation (RMSD) data between the native and mutant LKB1 structures, assessments utilizing Yet another Scientific Artificial Reality Application (YASARA) indicate a diminished binding affinity of the variant LKB1 to the STRAD protein compared to its native counterpart. Comparing the native and variant LKB1 tertiary structures showed misalignments upon superimposition.
RMSD data of various specific amino acid residues exhibited disparities of more than 2 angstroms. Additionally, discernible variances in the positioning of cavity pockets are observed between the native and variant LKB1 proteins. Collectively, the analytical findings suggest that the D176A mutation in the LKB1 protein is likely to entail detrimental consequences.
Published Date: 2024-09-02; Received Date: 2024-08-02