In Silico Study of Human Gap Junction Beta-2 Protein by Homology Modeling

Abstract

Abstract Asp66his, Asp54Lys, and Asp50Asn are mutations in connexin 26 that are observed in the clinic and give rise to autosomal dominant syndromes. They are the result of point mutations in the human gap junction β-2 gene. In order to investigate the structural mechanism of Bart-Pumphrey Syndrome, Keratitis-Ichthyosis-Deafness Syndrome, and Vohwinkel Syndrome, homology model-ing was carried out. Asp66 has direct contact with Asn62 by two hydrogen bonds in the wild-type protein, and in Asp66His, the biggest change observed is a tre-mendous energy increase caused by hydrogen bond breakage to Asn62. Shifts in the side chain and new hy-drogen bond formation are observed for Lys54 com-pared to the wild-type protein (Asn54) and result in clos-er contact to Val84. Asp50Asn causes a significant de-crease in bond energy, and residual charge reversal re-pels the ion and metabolites and, hence, inhibits their transportation. Such perturbations are likely to be a fac-tor contributing to abnormal functioning of ion channels, resulting cell death and disease.Keywords: Bart-Pumphrey syndrome, connexin 26, gap junction, β-2 protein, hearing impairment, Keratitis-Ich-thyosis-Deafness syndrome, knuckle pads, leukonychia, vohwinkel syndrome