Chaperone-like activity of alpha-cyclodextrin via hydrophobic nanocavity to protect native structure of ADH.
The chaperone action of alpha-cyclodextrin (alpha-CyD), based on providing beneficial microenvironment of hydrophobic nanocavity to form molecular complex with alcohol dehydrogenase (ADH) was examined by experimental and computational techniques. The results of UV-vis and dynamic light scattering (DLS) indicated that the chaperone-like activity of alpha-CyD depends on molecular complex formation between alpha-CyD and ADH, which caused to decrease the amount and size of polymerized molecules. Computational calculations of molecular dynamic (MD) simulations and blind docking (BD) demonstrated that alpha-CyD acts as an artificial chaperone because of its high affinity to the region of ADH's two chains interface. The hydrophobic nanocavity of alpha-CyD has the ability to form inclusion complex due to the presence of phenyl ring of aromatic phenylalanine (Phe) residue in the dimeric intersection area. Delocalization of ADH subunits, which causes the exposure of Phe110, takes part in the enzyme polymerization and has proven to be beneficial for aggregation inhibition and solubility enhancement within the host alpha-CyD-nanocavity.
Barzegar
Abolfazl
A
Research Institute for Fundamental Sciences, University of Tabriz, Tabriz, Iran. barzegar@tabrizu.ac.ir
Moosavi-Movahedi
Ali A
AA
Mahnam
Karim
K
Ashtiani
Saman Hosseini
SH
D000426:Alcohol Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D015195:Drug Design; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D018832:Molecular Chaperones / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D049329:Nanostructures; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D047391:alpha-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism*
D008024:Ligands; D018832:Molecular Chaperones; D047391:alpha-Cyclodextrins; D000426:Alcohol Dehydrogenase