Docking of human rhodopsin mutant (Gly90→Asp) with beta-arrestin and cyanidin 3-rutinoside to cure night blindness.

Shagufta Kanwal,Sumaira Nishat,Muhammad Irfan Khan

doi:10.6026/97320630008128

Shagufta Kanwal, Sumaira Nishat + Show 1 more

Open Access

https://doi.org/10.6026/97320630008128

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Journal: Bioinformation	Publication Date: Feb 3, 2012
Citations: 2	License type: cc-by

Affiliation: International Islamic University, Islamabad

Abstract

Rhodopsin is a visual pigment present in rod cells of retina. It belongs to GPCR family and involves photoisomerization of 11-cis-retinal to all-trans-retinal isomers, conformational changes in rhodopsin and signal transduction cascade to generate a nerve impulse. This signaling pathway has been targeted to eliminate the effect of a mutation (Gly90→Asp) responsible for abnormal activation of G-protein without retinal conformations in the absence of light leading to congenital night blindness. A theoretical model of rhodopsin with induced mutation has been deliberated in order to find potential ligands which can offset this mutational effect. The binding interactions between the target mutated rhodopsin model and potential ligands have been predicted with the help of molecular docking. The results indicated strong functional benefits of ligands as an inhibitor and an agonist for mutated rhodopsin model. Therefore, we propose a new visual cascade model which can initiate the normal signaling of rhodopsin mutant with the help of proposed ligands and can provide a hope for vision in future.

Highlights

In binding of agonist with GPCR proteins cause conformational vitro experiments suggest that transducin is activated by the changes in its structure
GPCRs undergo multiple conformational changes upon agonist binding so new agonist exploration and development is in progress possibly through docking techniques [4]
The mutant rhodopsin was first docked with its native ligand “cis-retinal” so that its native binding pocket can be conserved and other candidate ligands can be docked in suitable orientation in the predicted binding sites

Summary

Introduction

In binding of agonist with GPCR proteins cause conformational vitro experiments suggest that transducin is activated by the changes in its structure. A model of interaction for the human Arrestin-Rhodopsin complex has been obtained by a protein docking approach, reinforced by experimental data and binding energy calculation [7].

Results

Conclusion