PMID- 29298351
OWN - NLM
STAT- MEDLINE
DCOM- 20180215
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 1
DP  - 2018
TI  - Functional consequences of piceatannol binding to glyceraldehyde-3-phosphate 
      dehydrogenase.
PG  - e0190656
LID - 10.1371/journal.pone.0190656 [doi]
LID - e0190656
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the key 
      redox-sensitive proteins whose activity is largely affected by oxidative 
      modifications at its highly reactive cysteine residue in the enzyme's active site 
      (Cys149). Prolonged exposure to oxidative stress may cause, inter alia, the 
      formation of intermolecular disulfide bonds leading to accumulation of GAPDH 
      aggregates and ultimately to cell death. Recently these anomalies have been 
      linked with the pathogenesis of Alzheimer's disease. Novel evidences indicate 
      that low molecular compounds may be effective inhibitors potentially preventing 
      the GAPDH translocation to the nucleus, and inhibiting or slowing down its 
      aggregation and oligomerization. Therefore, we decided to establish the ability 
      of naturally occurring compound, piceatannol, to interact with GAPDH and to 
      reveal its effect on functional properties and selected parameters of the 
      dehydrogenase structure. The obtained data revealed that piceatannol binds to 
      GAPDH. The ITC analysis indicated that one molecule of the tetrameric enzyme may 
      bind up to 8 molecules of polyphenol (7.3 +/- 0.9). Potential binding sites of 
      piceatannol to the GAPDH molecule were analyzed using the Ligand Fit algorithm. 
      Conducted analysis detected 11 ligand binding positions. We indicated that 
      piceatannol decreases GAPDH activity. Detailed analysis allowed us to presume 
      that this effect is due to piceatannol ability to assemble a covalent binding 
      with nucleophilic cysteine residue (Cys149) which is directly involved in the 
      catalytic reaction. Consequently, our studies strongly indicate that piceatannol 
      would be an exceptional inhibitor thanks to its ability to break the 
      aforementioned pathologic disulfide linkage, and therefore to inhibit GAPDH 
      aggregation. We demonstrated that by binding with GAPDH piceatannol blocks 
      cysteine residue and counteracts its oxidative modifications, that induce 
      oligomerization and GAPDH aggregation.
FAU - Gerszon, Joanna
AU  - Gerszon J
AUID- ORCID: 0000-0001-9754-4108
AD  - Department of Molecular Biophysics, Faculty of Biology and Environmental 
      Protection, University of Lodz, Lodz, Poland.
AD  - Bionanopark Ltd., Lodz, Poland.
FAU - Serafin, Eligiusz
AU  - Serafin E
AD  - Laboratory of Computer and Analytical Techniques, Faculty of Biology and 
      Environmental Protection, University of Lodz, Lodz, Poland.
FAU - Buczkowski, Adam
AU  - Buczkowski A
AD  - Unit of Biophysical Chemistry, Department of Physical Chemistry, Faculty of 
      Chemistry, University of Lodz, Lodz, Poland.
FAU - Michlewska, Sylwia
AU  - Michlewska S
AD  - Department of General Biophysics, Faculty of Biology and Environmental 
      Protection, University of Lodz, Lodz, Poland.
AD  - Laboratory of Microscopic Imaging and Specialized Biological Techniques, Faculty 
      of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
FAU - Bielnicki, Jakub Antoni
AU  - Bielnicki JA
AD  - Bionanopark Ltd., Lodz, Poland.
FAU - Rodacka, Aleksandra
AU  - Rodacka A
AD  - Department of Molecular Biophysics, Faculty of Biology and Environmental 
      Protection, University of Lodz, Lodz, Poland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180103
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ligands)
RN  - 0 (Stilbenes)
RN  - 6KS3LS0D4F (3,3',4,5'-tetrahydroxystilbene)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Calorimetry
MH  - Catalytic Domain
MH  - Circular Dichroism
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/chemistry/*metabolism
MH  - Hydrogen Peroxide/metabolism
MH  - Ligands
MH  - Microscopy, Electron, Transmission
MH  - Models, Molecular
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Stilbenes/*metabolism
PMC - PMC5752021
COIS- Competing Interests: The involvement of Bionanopark Ltd. does not alter our 
      adherence to PLOS ONE policies on sharing data and materials.
EDAT- 2018/01/04 06:00
MHDA- 2018/02/16 06:00
PMCR- 2018/01/03
CRDT- 2018/01/04 06:00
PHST- 2017/09/20 00:00 [received]
PHST- 2017/12/18 00:00 [accepted]
PHST- 2018/01/04 06:00 [entrez]
PHST- 2018/01/04 06:00 [pubmed]
PHST- 2018/02/16 06:00 [medline]
PHST- 2018/01/03 00:00 [pmc-release]
AID - PONE-D-17-34199 [pii]
AID - 10.1371/journal.pone.0190656 [doi]
PST - epublish
SO  - PLoS One. 2018 Jan 3;13(1):e0190656. doi: 10.1371/journal.pone.0190656. 
      eCollection 2018.