Alzheimer’s disease (AD) is a progressive brain disorder. The accumulation of amyloid beta (Aβ) peptides in the human brain leads to AD. The cleavage of Aβ peptides by several enzymes is being considered as an essential aspect in the treatment of AD. Neprilysin (NEP) is an important enzyme that clears the Aβ plaques in the human brain. The human NEP activity has been found reduced due to mutations in NEP and the presence of inhibitors. However, the role of NEP in the degradation of Aβ peptides in detail at the molecular level is not yet clear. Hence, in the present study, we have investigated the structural significance of NEP from the bacterial source Streptococcus suis GZ1 using various bioinformatics approaches. The homology modelling technique was used to predict the three-dimensional structure of NEP. Further, molecular dynamic (MD) simulated model of NEP was docked with Aβ peptide. Analysis of MD simulated docked complex showed that the wild-type NEP-Aβ-peptide complex is more stable as compared to mutant complex. Hydrogen bonding interactions between NEP with Znand Aβ peptide confirm the degradation of the Aβ peptide. The molecular docking and MD simulation results revealed that the active site residue Glu-538 of bacterial NEP along with Zn interact with His-13 of Aβ peptide. This stable interaction confirms the involvement of NEP with Glu-538 in the degradation of the Aβ peptide. The other residues such as Glu203, Ser537, Gly140, Val587, and Val536 could also play an important role in the cleavage of Aβ peptide in between Asp1-Ala2, Arg5-His6, Val18-Phe19, Gly9-Tyr10, and Arg5-His6. Hence, the predicted model of the NEP enzyme of Streptococcus suis GZ1could be useful to understand the Aβ peptide degradation in detail at the molecular level. The information obtained from this study would be helpful in designing new lead molecules for the effective treatment of AD.
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