title: Amyloid beta modulated the selectivity of heme-catalyzed protein tyrosine nitration: an alternative mechanism for selective protein nitration.
abstract: Protein tyrosine nitration is a post-translational modification associated with numerous pathological conditions. The biological consequences of this modification strongly depend on the site selectivity. Unfortunately, to date there is still no reliable model for predicting the selectivity of protein tyrosine nitration. Previously, we found that amyloid beta (Aβ) changed the selectivity of enolase tyrosine nitration upon binding to heme. It seemed that there was a link between the hydrophilicity of Aβ and the site-specific tyrosine nitration. We further investigated the role of the hydrophilicity of the molecules that bind to heme in the selectivity of protein tyrosine nitration. We found that Aβ(1-16), Aβ(1-20), and Aβ(1-40), upon binding to heme and interacting with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in a site-specific manner, differently modulated the site selectivity of heme-catalyzed GAPDH tyrosine nitration. The modulation is associated with the hydrophilicity of the Aβ peptides, which changed the surrounding environment of the heme. At the same time, the Aβ-heme complexes were found to be more effective at inactivating GAPDH than heme alone, and the selective tyrosine nitration that was catalyzed by Aβ-heme played an important role. These findings suggest an alternative mechanism for the selectivity of protein tyrosine nitration, which may lead to a better understanding of the factors that influence protein tyrosine nitration selectivity and the important roles of Aβ and heme in the pathogenesis of Alzheimer's disease, where Aβ accumulation and Aβ-dependent protein nitration play central roles.
authors: School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
authors: Can
authors: C
authors: Yuan
authors: Hailing
authors: H
authors: Li
authors: Zhonghong
authors: Z
authors: Gao
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D015153:Blotting, Western; D002942:Circular Dichroism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry; D006420:Hemeproteins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D013058:Mass Spectrometry; D008958:Models, Molecular; D009566:Nitrates / Q000737:chemistry*; D010751:Phosphopyruvate Hydratase / Q000737:chemistry; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D006420:Hemeproteins; D009566:Nitrates; D014443:Tyrosine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010751:Phosphopyruvate Hydratase