Glycation of α-synuclein amplifies the binding with glyceraldehyde-3-phosphate dehydrogenase.
Int J Biol Macromol
; 127: 278-285, 2019 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-30658140
ABSTRACT
α-Synuclein was recently found to interact with moonlighting glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) involved in neurodegenerative diseases development. In the present work, we have analyzed influence of α-synuclein glycation on this interaction, because the literature data suggest relation between diabetes and Parkinson's disease. According to zeta potential measurement, glycation can shift the charge of α-synuclein to more negative values that was pronounced in case of modification by glyceraldehyde-3-phosphate. We selected carboxymethyl lysine as a typical advanced glycation end product and performed molecular dynamics simulations. The binding was found to be electrostatically driven and was significantly amplified after α-synuclein glycation because of increase the number of acidic residues. Since the main binding site was located in the anion-binding groove, which comprises the active site of GAPDH, enhanced binding of α-synuclein can result in GAPDH inactivation. This hypothesis was proven experimentally. Glycation of α-synuclein resulted in increase of GAPDH inactivation, and this effect was more pronounced in case of modification by glyceraldehyde-3-phosphate. The obtained results can reflect the probable relations between protein glycation and neurodegenerative diseases.
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Base de dados:
MEDLINE
Assunto principal:
Produtos Finais de Glicação Avançada
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Doenças Neurodegenerativas
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Alfa-Sinucleína
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Simulação de Dinâmica Molecular
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Gliceraldeído 3-Fosfato
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Gliceraldeído-3-Fosfato Desidrogenases
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article