Molecular insights into the binding mechanisms of human and mouse Glutamate-cysteine ligases

Background: the significant role of glutamate-cysteine ligase (GCL) towards the synthesis of glutathione for the sequestration of reactive species as a regulatory point is second to none. However, much still need to be known about the enzyme molecular characterization. Thus, the homology modeling of GCL was carried out using different modeling webserver tools. The quality of the predicted crystal structures of human and mouse GCLs with inhibition were further assessed on molecular interaction with naphthalene and its metabolites. Results: the predicted human GCL and mouse GCL model structures have respective 89.8% and 89.6% residues in the most favored region of the Ramachandran plot. However, the molecular docking interaction study with the assessed ligands revealed two different binding pockets with pi-interactions as major non-covalent bond and better binding scores than glutathione. Conclusion: the predicted model could provide better mechanism of GCL catalysis to preserve its essential residues for reasonable GSH synthesis.