An in-silico approach for finding inhibitor against Oxidoreductase enzyme from methanogeneic bacteria: A new way for inhibiting methanogenesis

Sarra Akermi, Sagar Barage, Ritushree Biswas, Subrata Sinha, Surabhi Johari, Anshul Nigam, Sunil Jayant

Abstract


Methane play crucial role  in global warming in which methane emissions contribution of ruminant  is substantial (~ 15%) due to presence of methanogens in their digestive system. Methanogens release large amount of methane into the environment via methanogenesis where, F420:NADP oxidoreductase catalyzes key step of  electron transfer between NADP+ and F420 in methanogenesis. Thus, F420:NADP oxidoreductase is crucual enzyme to regulate methane production in cattle. However, the structural detail of F420:NADP oxidoreductase is not available till date. Hence ,  we predicted  3D structure of F420:NADP oxidoreductase of M. barkeri and M. smithii using homology modeling technique. Subsequently, we screened herbal plant metabolities against predicted models of F420:NADP oxidoreductase from M. barkeri and M. smithii followed by MD simulation. Molecular docking and MD simulation studies  revealed that, saponin   efficiently accommodate in NADP binding cavity of enzyme and shows  lowest binding free  energy than other metabolites. Furthermore, F420:NADP oxidoreductase enzyme residues T90, R92, M119, K121, R160, R163, K223, K228 and V117  involvedin hydrogen  bonding and hydrophobic interaction with saponin. Overall, saponin could be used as potential inhibitor for Oxidoreductase enzyme  to control methanogenesis.


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