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

Abstract

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 (Fe2+) and oxidized
state (Fe3+) 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.