期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 127, 期 -, 页码 278-285出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2019.01.064
关键词
alpha-Synuclein; Glyceraldehyde-3-phosphate dehydrogenase; Glycation
资金
- Russian Science Foundation [16-14-10027]
- Russian Science Foundation [19-14-13009] Funding Source: Russian Science Foundation
alpha-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 alpha-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 alpha-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 alpha-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 alpha-synuclein can result in GAPDH inactivation. This hypothesis was proven experimentally. Glycation of alpha-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. (C) 2019 Elsevier B.V. All rights reserved.
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