Rifampicin: a glucocorticoid receptor ligand?

10.1038/2575 ◽  
1998 ◽  
Vol 4 (10) ◽  
pp. 1090-1090 ◽  
Author(s):  
D.W. Ray ◽  
A.M. Lovering ◽  
J.R.E. Davis ◽  
A. White
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Ligand

scholarly journals Cell Type-Dependent Divergence of Transactivation by Glucocorticoid Receptor Ligand

2002 ◽  
Vol 25 (12) ◽  
pp. 1619-1622 ◽  
Author(s):  
Kiyoshi Tanigawa ◽  
Katsunao Tanaka ◽  
Hideki Nagase ◽  
Hidekazu Miyake ◽  
Mamoru Kiniwa ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Cell Type ◽  
Receptor Ligand

scholarly journals Test systems for the determination of glucocorticoid receptor ligand induced skin atrophy

2011 ◽  
Vol 3 (3) ◽  
pp. 175-179 ◽  
Author(s):  
Stefanie Schoepe ◽  
Heike Schäcke ◽  
Khusru Asadullah
Keyword(s):  
Glucocorticoid Receptor ◽  
Skin Atrophy ◽  
Receptor Ligand ◽  
Test Systems

scholarly journals Therapeutic and Adverse Effects of a Non-Steroidal Glucocorticoid Receptor Ligand in a Mouse Model of Multiple Sclerosis

PLoS ONE ◽  
2009 ◽  
Vol 4 (12) ◽  
pp. e8202 ◽  
Author(s):  
Simone Wüst ◽  
Denise Tischner ◽  
Michael John ◽  
Jan P. Tuckermann ◽  
Christiane Menzfeld ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Effects ◽  
Mouse Model ◽  
Glucocorticoid Receptor ◽  
Receptor Ligand

scholarly journals Alternate glucocorticoid receptor ligand binding structures influence outcomes in an in vivo tissue regeneration model

2012 ◽  
Vol 156 (2) ◽  
pp. 121-129 ◽  
Author(s):  
Sumitra Sengupta ◽  
William H. Bisson ◽  
Lijoy K. Mathew ◽  
Siva K. Kolluri ◽  
Robert L. Tanguay
Keyword(s):  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Tissue Regeneration ◽  
Receptor Ligand

scholarly journals Doubling the Size of the Glucocorticoid Receptor Ligand Binding Pocket by Deacylcortivazol

2007 ◽  
Vol 28 (6) ◽  
pp. 1915-1923 ◽  
Author(s):  
Kelly Suino-Powell ◽  
Yong Xu ◽  
Chenghai Zhang ◽  
Yong-guang Tao ◽  
W. David Tolbert ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Binding Pocket ◽  
Affinity Binding ◽  
Receptor Ligand ◽  
Ligand Binding Pocket ◽  
Steroid Receptor Coactivator ◽  
High Affinity ◽  
Binding Domains ◽  
Lxxll Motif

ABSTRACT A common feature of nuclear receptor ligand binding domains (LBD) is a helical sandwich fold that nests a ligand binding pocket within the bottom half of the domain. Here we report that the ligand pocket of glucocorticoid receptor (GR) can be continuously extended into the top half of the LBD by binding to deacylcortivazol (DAC), an extremely potent glucocorticoid. It has been puzzling for decades why DAC, which contains a phenylpyrazole replacement at the conserved 3-ketone of steroid hormones that are normally required for activation of their cognate receptors, is a potent GR activator. The crystal structure of the GR LBD bound to DAC and the fourth LXXLL motif of steroid receptor coactivator 1 reveals that the GR ligand binding pocket is expanded to a size of 1,070 Å3, effectively doubling the size of the GR dexamethasone-binding pocket of 540 Å3 and yet leaving the structure of the coactivator binding site intact. DAC occupies only ∼50% of the space of the pocket but makes intricate interactions with the receptor around the phenylpyrazole group that accounts for the high-affinity binding of DAC. The dramatic expansion of the DAC-binding pocket thus highlights the conformational adaptability of GR to ligand binding. The new structure also allows docking of various nonsteroidal ligands that cannot be fitted into the previous structures, thus providing a new rational template for drug discovery of steroidal and nonsteroidal glucocorticoids that can be specifically designed to reach the unoccupied space of the expanded pocket.

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