PMID- 30658140
OWN - NLM
STAT- MEDLINE
DCOM- 20190619
LR  - 20190619
IS  - 1879-0003 (Electronic)
IS  - 0141-8130 (Linking)
VI  - 127
DP  - 2019 Apr 15
TI  - Glycation of alpha-synuclein amplifies the binding with glyceraldehyde-3-phosphate 
      dehydrogenase.
PG  - 278-285
LID - S0141-8130(18)36292-5 [pii]
LID - 10.1016/j.ijbiomac.2019.01.064 [doi]
AB  - 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.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Semenyuk, Pavel
AU  - Semenyuk P
AD  - Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State 
      University, Moscow, Russia. Electronic address: psemenyuk@belozersky.msu.ru.
FAU - Barinova, Kseniya
AU  - Barinova K
AD  - Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State 
      University, Moscow, Russia.
FAU - Muronetz, Vladimir
AU  - Muronetz V
AD  - Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State 
      University, Moscow, Russia; Faculty of Bioengineering and Bioinformatics, 
      Lomonosov Moscow State University, Moscow, Russia.
LA  - eng
PT  - Journal Article
DEP - 20190115
PL  - Netherlands
TA  - Int J Biol Macromol
JT  - International journal of biological macromolecules
JID - 7909578
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (SNCA protein, human)
RN  - 0 (alpha-Synuclein)
RN  - 142-10-9 (Glyceraldehyde 3-Phosphate)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Catalytic Domain
MH  - *Glycation End Products, Advanced/chemistry/metabolism
MH  - *Glyceraldehyde 3-Phosphate/chemistry/metabolism
MH  - *Glyceraldehyde-3-Phosphate Dehydrogenases/chemistry/metabolism
MH  - Glycosylation
MH  - Humans
MH  - *Molecular Dynamics Simulation
MH  - Neurodegenerative Diseases/*metabolism
MH  - *alpha-Synuclein/chemistry/metabolism
OTO - NOTNLM
OT  - Glycation
OT  - Glyceraldehyde-3-phosphate dehydrogenase
OT  - alpha-Synuclein
EDAT- 2019/01/19 06:00
MHDA- 2019/06/20 06:00
CRDT- 2019/01/19 06:00
PHST- 2018/11/18 00:00 [received]
PHST- 2019/01/14 00:00 [revised]
PHST- 2019/01/14 00:00 [accepted]
PHST- 2019/01/19 06:00 [pubmed]
PHST- 2019/06/20 06:00 [medline]
PHST- 2019/01/19 06:00 [entrez]
AID - S0141-8130(18)36292-5 [pii]
AID - 10.1016/j.ijbiomac.2019.01.064 [doi]
PST - ppublish
SO  - Int J Biol Macromol. 2019 Apr 15;127:278-285. doi: 
      10.1016/j.ijbiomac.2019.01.064. Epub 2019 Jan 15.