Insights into the molecular interactions between aminopeptidase and amyloid beta peptide using molecular modeling techniques
Amyloid beta (Aβ) peptides play a central role in the pathogenesis of Alzheimer’s disease. The accumulation of Aβ peptides in AD brain was caused due to overproduction or insufficient clearance and defects in the proteolytic degradation of Aβ peptides. Hence, Aβ peptide degradation could be a promising therapeutic approach in AD treatment. Recent experimental report suggests that aminopeptidase from Streptomyces griseus KK565 (SGAK) can degrade Aβ peptides but the interactive residues are yet to be known in detail at the atomic level. Hence, we developed the three-dimensional model of aminopeptidase (SGAK) using SWISS-MODEL, Geno3D and MODELLER. Model built by MODELLER was used for further studies. Molecular docking was performed between aminopeptidase (SGAK) with wild-type and mutated Aβ peptides. The docked complex of aminopeptidase (SGAK) and wild-type Aβ peptide (1IYT.pdb) shows more stability than the other complexes. Molecular docking and MD simulation results revealed that the residues His93, Asp105, Glu139, Glu140, Asp168 and His255 are involved in the hydrogen bonding with Aβ peptide and zinc ions. The interactions between carboxyl oxygen atoms of Glu139 of aminopeptidase (SGAK) with water molecule suggest that the Glu139 may be involved in the nucleophilic attack on Ala2–Glu3 peptide bond of Aβ peptide. Hence, amino acid Glu139 of aminopeptidase (SGAK) might play an important role to degrade Aβ peptides, a causative agent of Alzheimer’s disease.
KeywordsAlzheimer’s disease Amyloid beta (Aβ) Aminopeptidases (APNs) Molecular docking and MD simulations
- Aβ peptide
Amyloid beta peptide
Aminopeptidase from Streptomyces griseus strain KK565
Root mean square deviation
MJD is thankful to Department of Science and Technology, New Delhi for providing fellowship as research assistance under the scheme DST-PURSE. KDS is thankful to the Department of Biotechnology, New Delhi for financial support under the scheme DBT-IPLS sanctioned to Shivaji University, Kolhapur. Authors are thankful to Computer Centre, Shivaji University, Kolhapur for providing the computational facility.
Conflict of interest
All authors have no conflict of interest.
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