title: Heme binding site in apomyoglobin may be effectively targeted with small molecules to control aggregation.
abstract: A number of ligands with affinities for the heme binding site of apomyoglobin were tested to control amorphous and fibrillar aggregation in the protein. Several techniques, including fluorescence, dynamic light scattering, transmission electron microscopy, dot blot analysis combined with viability studies were employed for structural characterization and cytotoxicity assessment of the intermediate and final protein structures formed during the aggregation process. Of the small molecules investigated, chrysin and Nile red with high structural similarities to heme were chosen for further studies. Only fibril formation was found to be prevented by Nile red, while chrysin, with a greater structural flexibility, was able to prevent both types of aggregate formation. The two ligands were found to influence aggregation at different stages of intermediate structure formation, an ability determined by their degrees of similarities with heme. Based on structural characterization and toxicity studies, it is concluded that ligands similar in structure to heme may be effective in influencing various stages of aggregate formation and toxicity potencies of the protein structures. Since metalloproteins constitute more than thirty percent of all known proteins, it is concluded that the present strategy may be of general significance.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, PO Box 13145-1384, 1417614411 Tehran, Iran.
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Azami-Movahed
authors.forename: Sajad
authors.initials: S
authors.lastname: Shariatizi
authors.forename: Marjan
authors.initials: M
authors.lastname: Sabbaghian
authors.forename: Atiyeh
authors.initials: A
authors.lastname: Ghasemi
authors.forename: Azadeh
authors.initials: A
authors.lastname: Ebrahim-Habibi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nemat-Gorgani
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000502:physiology; D000818:Animals; D001059:Apoproteins / Q000737:chemistry* / Q000502:physiology; D052160:Benzothiazoles; D001665:Binding Sites; D002470:Cell Survival; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D006418:Heme / Q000737:chemistry*; D006736:Horses; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008027:Light; D062105:Molecular Docking Simulation; D009211:Myoglobin / Q000737:chemistry* / Q000502:physiology; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D010316:Particle Size; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D051381:Rats; D012542:Scattering, Radiation; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000682:Amyloid; D001059:Apoproteins; D052160:Benzothiazoles; D005419:Flavonoids; D005456:Fluorescent Dyes; D009211:Myoglobin; D010078:Oxazines; D013844:Thiazoles; C010857:apomyoglobin; C009462:thioflavin T; C043561:chrysin; D006418:Heme; C044808:nile red