Ghent University Academic Bibliography

Advanced

Inhibition of Heterotrimeric G Protein Signaling by a Small Molecule Acting on G alpha Subunit

MA Ayoub, M Damian, C Gespach, E Ferrandis, O Lavergne, Olivier De Wever UGent, JL Baneres, JP Pin and GP Prevost (2009) JOURNAL OF BIOLOGICAL CHEMISTRY. 284(42). p.29136-29145
abstract
The simultaneous activation of many distinct G protein-coupled receptors (GPCRs) and heterotrimeric G proteins play a major role in various pathological conditions. Pan-inhibition of GPCR signaling by small molecules thus represents a novel strategy to treat various diseases. To better understand such therapeutic approach, we have characterized the biomolecular target of BIM-46187, a small molecule pan-inhibitor of GPCR signaling. Combining bioluminescence and fluorescence resonance energy transfer techniques in living cells as well as in reconstituted receptor-G protein complexes, we observed that, by direct binding to the G alpha subunit, BIM-46187 prevents the conformational changes of the receptor-G protein complex associated with GPCR activation. Such a binding prevents the proper interaction of receptors with the G protein heterotrimer and inhibits the agonist-promoted GDP/GTP exchange. These observations bring further evidence that inhibiting G protein activation through direct binding to the G alpha subunit is feasible and should constitute a new strategy for therapeutic intervention.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
J. Biol. Chem.
volume
284
issue
42
pages
29136 - 29145
Web of Science type
Article
Web of Science id
000270678900069
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
5.328 (2009)
JCR rank
48/281 (2009)
JCR quartile
1 (2009)
ISSN
0021-9258
DOI
10.1074/jbc.M109.042333
language
English
UGent publication?
yes
classification
A1
id
849942
handle
http://hdl.handle.net/1854/LU-849942
date created
2010-02-02 16:42:15
date last changed
2010-02-12 16:02:28
@article{849942,
  abstract     = {The simultaneous activation of many distinct G protein-coupled receptors (GPCRs) and heterotrimeric G proteins play a major role in various pathological conditions. Pan-inhibition of GPCR signaling by small molecules thus represents a novel strategy to treat various diseases. To better understand such therapeutic approach, we have characterized the biomolecular target of BIM-46187, a small molecule pan-inhibitor of GPCR signaling. Combining bioluminescence and fluorescence resonance energy transfer techniques in living cells as well as in reconstituted receptor-G protein complexes, we observed that, by direct binding to the G alpha subunit, BIM-46187 prevents the conformational changes of the receptor-G protein complex associated with GPCR activation. Such a binding prevents the proper interaction of receptors with the G protein heterotrimer and inhibits the agonist-promoted GDP/GTP exchange. These observations bring further evidence that inhibiting G protein activation through direct binding to the G alpha subunit is feasible and should constitute a new strategy for therapeutic intervention.},
  author       = {Ayoub, MA and Damian, M and Gespach, C and Ferrandis, E and Lavergne, O and De Wever, Olivier and Baneres, JL and Pin, JP and Prevost, GP},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  language     = {eng},
  number       = {42},
  pages        = {29136--29145},
  title        = {Inhibition of Heterotrimeric G Protein Signaling by a Small Molecule Acting on G alpha Subunit},
  url          = {http://dx.doi.org/10.1074/jbc.M109.042333},
  volume       = {284},
  year         = {2009},
}

Chicago
Ayoub, MA, M Damian, C Gespach, E Ferrandis, O Lavergne, Olivier De Wever, JL Baneres, JP Pin, and GP Prevost. 2009. “Inhibition of Heterotrimeric G Protein Signaling by a Small Molecule Acting on G Alpha Subunit.” Journal of Biological Chemistry 284 (42): 29136–29145.
APA
Ayoub, M., Damian, M., Gespach, C., Ferrandis, E., Lavergne, O., De Wever, O., Baneres, J., et al. (2009). Inhibition of Heterotrimeric G Protein Signaling by a Small Molecule Acting on G alpha Subunit. JOURNAL OF BIOLOGICAL CHEMISTRY, 284(42), 29136–29145.
Vancouver
1.
Ayoub M, Damian M, Gespach C, Ferrandis E, Lavergne O, De Wever O, et al. Inhibition of Heterotrimeric G Protein Signaling by a Small Molecule Acting on G alpha Subunit. JOURNAL OF BIOLOGICAL CHEMISTRY. 2009;284(42):29136–45.
MLA
Ayoub, MA, M Damian, C Gespach, et al. “Inhibition of Heterotrimeric G Protein Signaling by a Small Molecule Acting on G Alpha Subunit.” JOURNAL OF BIOLOGICAL CHEMISTRY 284.42 (2009): 29136–29145. Print.