title: Effect of Structural Changes in Proteins Derived from GATA4 Nonsynonymous Single Nucleotide Polymorphisms in Congenital Heart Disease.
abstract: Congenital heart disease is the most common type of birth defect. The single nucleotide polymorphism in GATA4 is associated with various congenital heart disease phenotypes. In the present study, we analysed the nonsynonymous single nucleotide polymorphism of GATA4, which are involved in congenital heart disease by predicting the changes in protein structures. Total of 49 nonsynonymous single nucleotide polymorphisms of GATA4 was screened from congenital heart disease patients of Mysore and also globally reported nonsynonymous single nucleotide polymorphisms. To understand the role of nonsynonymous single nucleotide polymorphisms, we mutated the sequence and translated into amino acids. Further the mutated protein secondary structure is predicted and tertiary structure is predicted using homology modeling. The quantitative evaluation of protein structure quality was verified with Volume Area Dihedral Angle Reporter server. Results revealed the secondary, tertiary structural changes along with changes in free energy of folding, volume and accessible surface area. Thus, the structural changes in the mutated proteins impaired the normal function of GATA4.
authors.affiliation: NUCSER, K S Hegde Medical Academy, NITTE University, Deralakatte, Mangalore-575 018, India.
authors.forename: D S
authors.initials: DS
authors.lastname: Manjegowda
authors.affiliation: Department of Biotechnology, PES Institute of Technology, BSK III Stage, Bengaluru-560 085, India, India.
authors.forename: P
authors.initials: P
authors.lastname: Karunakar
authors.affiliation: Department of Studies in Zoology, Genomics Laboratory, University of Mysore, Manasagangotri, Mysore-570 006, India.
authors.forename: N B
authors.initials: NB
authors.lastname: Ramachandra
keywords: Congenital heart disease; GATA4; free energy folding; homology modeling; single nucleotide polymorphism