TITLE:
In silico analysis of influence of the missense mutation P629S on the molecular interaction and 3D properties of PIK3R5
AUTHORS:
Jameela Shinwari, Asma I. Tahir, Saeed Bohlega, Nada AlTassan
KEYWORDS:
PIK3R5; Missense Mutation; Protein Modelling; Protein-Protein Docking; PIK3CG; Gβγ
JOURNAL NAME:
Advances in Biological Chemistry,
Vol.3 No.4,
August
9,
2013
ABSTRACT: PIK3R5 is the regulatory subunit of Phosphoinositide 3-kinase γ (PI3Kγ) that is responsible for phosphory-lating membrane lipids to activate the AKT pathway. PIK3R5 binds Gβγ and facilitates the interaction with p110γ catalytic subunit (PIK3CG) during PI3Kγ activation. The identification of PIK3R5 P629S mutation in AOA2 patients indicated a potential defect in the AKT pathway resulting from impaired PIK3R5 interaction with Gβγ and PIK3CG, defective AKT pathway can result in cerebellar cell death causing neurological symptoms. Our in silico macromolecular docking of the wild type and mutant PIK3R5 protein models with ligand revealed an energy requirement to maintain the mutant complexes compared to no energy required to maintain the wild type complexes, in addition, the mutant structures were loose compared to rigid wild type structures, such structural changes may impair the molecular function of the PIK3R5 and hence affect the AKT pathway.