title: Key roles of Arg(5), Tyr(10) and his residues in Aβ-heme peroxidase: relevance to Alzheimer's disease.
abstract: Recent reports show that heme binds to amyloid β-peptide (Aβ) in the brain of Alzheimer's disease (AD) patients and forms Aβ-heme complexes, thus leading a pathological feature of AD. However, the important biological relevance to AD etiology, resulting from human Aβ-heme peroxidase formation, was not well characterized. In this study, we used wild-type and mutated human Aβ1-16 peptides and investigated their Aβ-heme peroxidase activities. Our results indicated that both histidine residues (His(13), His(14)) in Aβ1-16 and free histidine enhanced the peroxidase activity of heme, hence His residues were essential in peroxidase activity of Aβ-heme complexes. Moreover, Arg(5) was found to be the key residue in making the Aβ1-16-heme complex as a peroxidase. Under oxidative and nitrative stress conditions, the Aβ1-16-heme complexes caused oxidation and nitration of the Aβ Tyr(10) residue through promoting peroxidase-like reactions. Therefore, these residues (Arg(5), Tyr(10) and His) were pivotal in human Aβ-heme peroxidase activity. However, three of these residues (Arg(5), Tyr(10) and His(13)) identified in this study are all absent in rodents, where rodent Aβ-heme complex lacks peroxidase activity and it does not show AD, implicating the novel significance of these residues as well as human Aβ-heme peroxidase in the pathology of AD.
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China. Electronic address: naihaolu@gmail.com.
authors.forename: Naihao
authors.initials: N
authors.lastname: Lu
authors.affiliation: Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China. Electronic address: yiyuanpeng@yahoo.com.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Peng
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D001120:Arginine / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D010544:Peroxidases / Q000737:chemistry*; D012996:Solutions; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012996:Solutions; C433241:amyloid beta-protein (1-16); C078592:amyloid beta-protein (1-40); D014443:Tyrosine; D006418:Heme; D006639:Histidine; D001120:Arginine; D010544:Peroxidases
keywords: Amyloid β-peptide; Aβ–heme peroxidase; Heme; Neurochemistry; Oxidation