Crystal structure and interaction of phycocyanin with β-secretase: A putative therapy for Alzheimer's disease.

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TitleCrystal structure and interaction of phycocyanin with β-secretase: A putative therapy for Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsSingh, NKumar, S Hasan, S, Kumar, J, Raj, I, Pathan, AA, Parmar, A, Shakil, S, Gourinath, S, Madamwar, D
JournalCNS Neurol Disord Drug Targets
Date Published2014
KeywordsAlzheimer Disease, Amyloid Precursor Protein Secretases, Animals, Animals, Genetically Modified, Bacterial Proteins, Caenorhabditis elegans, Cyanobacteria, Disease Models, Animal, Molecular Docking Simulation, Neuroprotective Agents, Paralysis, Phycocyanin, Protein Conformation, X-Ray Diffraction

Alzheimer's disease (AD) represents a neurological disorder, which is caused by enzymatic degradation of an amyloid precursor protein into short peptide fragments that undergo association to form insoluble plaques. Preliminary studies suggest that cyanobacterial extracts, especially the light-harvesting protein phycocyanin, may provide a means to control the progression of the disease. However, the molecular mechanism of disease control remains elusive. In the present study, intact hexameric phycocyanin was isolated and crystallized from the cyanobacterium Leptolyngbya sp. N62DM, and the structure was solved to a resolution of 2.6 A. Molecular docking studies show that the phycocyanin αβ-dimer interacts with the enzyme β-secretase, which catalyzes the proteolysis of the amyloid precursor protein to form plaques. The molecular docking studies suggest that the interaction between phycocyanin and β-secretase is energetically more favorable than previously reported inhibitor-β-secretase interactions. Transgenic Caenorhabditis elegans worms, with a genotype to serve as an AD-model, were significantly protected by phycocyanin. Therefore, the present study provides a novel structure-based molecular mechanism of phycocyanin-mediated therapy against AD.

Alternate JournalCNS Neurol Disord Drug Targets
PubMed ID24576002