1gs4
From Proteopedia
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'''STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER''' | '''STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER''' | ||
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[[Category: Wegg, A.]] | [[Category: Wegg, A.]] | ||
[[Category: Zhao, X Y.]] | [[Category: Zhao, X Y.]] | ||
| - | [[Category: | + | [[Category: Cortisol/ cortisone response]] |
| - | [[Category: | + | [[Category: Human androgen receptor]] |
| - | [[Category: | + | [[Category: Ligand-binding domain]] |
| - | [[Category: | + | [[Category: Prostate cancer]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:56:23 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:56, 2 May 2008
STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER
Overview
The crystal structure of a mutant androgen receptor (AR) ligand-binding domain (LBD) in complex with the agonist 9alpha-fluorocortisol has been determined at 1.95 A resolution. This mutant AR contains two mutations (L701H and T877A) and was previously reported as a high-affinity cortisol/cortisone responsive AR (AR(ccr)) isolated from the androgen-independent human prostate cancer cell lines MDA PCa 2a and 2b (Zhao et al. Nature Med. 2000, 6, 703-6). The three-dimensional structure of the AR(ccr) LBD complexed with 9alpha-fluorocortisol shows the typical conformation of an agonist-bound nuclear receptor in which helix 12 is precisely positioned as a "lid" for the ligand-binding pocket. Binding of 9alpha-fluorocortisol to the AR(ccr) involves favorable hydrogen bond patterns on the C17 and C21 substituents of the ligand due to the mutations at 701 and 877 in the AR(ccr). Our studies provide the first structural explanation for the glucocorticoid activation of AR(ccr), which is important for the development of new therapeutic treatments for androgen-independent prostate cancer.
About this Structure
1GS4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR(ccr)) derived from an androgen-independent prostate cancer., Matias PM, Carrondo MA, Coelho R, Thomaz M, Zhao XY, Wegg A, Crusius K, Egner U, Donner P, J Med Chem. 2002 Mar 28;45(7):1439-46. PMID:11906285 Page seeded by OCA on Fri May 2 17:56:23 2008
