Modelling profile of onchocerca volvulus glutamatecysteine ligase (ONCVO-GCL)

Onchocerca volvulus Glutamate cysteine ligase (ONCVO-GCL) catalyzes the first step in the production of the cellular antioxidant glutathione (GSH), which involve the condensation of cysteine and glutamate to form the dipeptide gamma-glutamylcysteine (γ-GC). ONCVO-GCL is critical to cell survival. Its dysregulation could lead to decreased GSH biosynthesis, reduced cellular antioxidant capacity, and the induction of oxidative stress. ONCVO-GCL expression support the high level of cell proliferation and confer resistance to many chemotherapeutic agents, hence could serve as a molecular target for inhibitors. This study aims to model the 3-dimensional (3D) structure of ONCVO-GCL, validate and predict the active sites of the modelled protein. ONCVO-GCL (Uniprot ID: A0A044QR48) 3D structure was modelled and validated using SWISS-MODEL. The Computed Atlas of Surface Topography of proteins (CASTp) 3.0 was used to predict the active sites of the modelled protein. A percentage identity matrix of 41.81% was obtained, which confirms the similarity identity of 40.86% obtained from the homology modelling. Model with 88% in the most favoured region of Ramachandra plot was obtained and the more favourable active sites for docking analyses due to the similarities observed from the alignment of the modelled structure to the template structure were: GLY 2A, LEU3A, LEU 4A, ARG 40A, TRP 47A, GLY 48A, ASP 49A, GLU 50A, GLU 52A, and PRO 109A.