Elucidating the precise interaction of reduced and oxidized states of Neuroglobin with Ubc12 and Cop9 using molecular mechanics studies

BACKGROUD & OBJECTIVE: Neuroglobin is an oxygen binding globin protein highly expressed in neurons. It is an iron containing heme protein, that exist in both ferrous and ferric form. Recent studies have indicated its role as an endogenous neuroprotective molecule. It is proposed that neuroglobin undergoes post-translational modification by the process of neddylation and deneddylation. Hence in this study an attempt was made to investigate the mode and mechanism of interaction of ferrous and ferric forms of neuroglobin with Ubc12 and op9, proteins involved in regulation of neddylation and deneddylation respectively, utilizing molecular modelling calculations. METHODOLOGY: In this study, the mode of interactions of Ubc12 and Cop9 with the reduced (Fe 2+ ) and oxidized state (Fe 3+ ) of neuroglobin was carried out using ZDock. The top scoring poses for each complex were subjected to energy minimization using CHARMM Polar H force field in RDock to obtain the binding affinities. RESULTS: The binding affinities between of ferrous and ferric forms of neuroglobin with Ubc12 and Cop9 were calculated. CONCLUSION: Results obtained strongly indicate that both Ubc12 and Cop9 interacts with neuroglobin in regulation of neddylation and deneddylation process. Furthermore these results guided us in precisely designing experiments for biological evaluations.