title: Peroxidase to Cytochrome b Type Transition in the Active Site of Heme-Bound Amyloid β Peptides Relevant to Alzheimer's Disease.
abstract: Recent evidence has established the colocalization of amyloid-rich plaques and heme-rich deposits in the human cerebral cortex as a common postmortem feature in Alzheimer's disease (AD). The amyloid β (Aβ) peptides have been shown to bind heme, and the resultant heme-Aβ complexes can generate toxic partially reduced oxygen species (PROS) and exhibit peroxidase activity. The heme-Aβ active site exhibits a concentration-dependent equilibrium between a high-spin mono-His-bound species similar to a peroxidase-type active site and a bis-His-bound six-coordinate low-spin species similar to that of a cytochrome b type active site. The ν(Fe-His) (241 cm(-1)) vibration has been identified in the high-spin heme-Aβ active site by resonance Raman spectroscopy. The formation of the low-spin heme-Aβ species is promoted by the His14 and noncoordinating second-sphere Arg5 residues. The high-spin state produces more PROS than the low-spin species. Nonbiological constructs modeling different forms of Aβ (oligomers, fibrils, etc.) suggest that the detrimental high-spin state is likely to dominate under most physiological conditions.
authors.affiliation: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700032, India.
authors.forename: Chandradeep
authors.initials: C
authors.lastname: Ghosh
authors.affiliation: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700032, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700032, India.
authors.forename: Manas
authors.initials: M
authors.lastname: Seal
authors.affiliation: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700032, India.
authors.forename: Somdatta Ghosh
authors.initials: SG
authors.lastname: Dey
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D020134:Catalytic Domain; D045303:Cytochromes b / Q000378:metabolism*; D006418:Heme / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides; D006418:Heme; D045303:Cytochromes b; D010544:Peroxidases