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1gs4

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{{STRUCTURE_1gs4| PDB=1gs4 | SCENE= }}
{{STRUCTURE_1gs4| PDB=1gs4 | SCENE= }}
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'''STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER'''
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===STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_11906285}}
==About this Structure==
==About this Structure==
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[[Category: Ligand-binding domain]]
[[Category: Ligand-binding domain]]
[[Category: Prostate cancer]]
[[Category: Prostate cancer]]
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Revision as of 02:59, 1 July 2008

Image:1gs4.png

Template:STRUCTURE 1gs4

STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER

Template:ABSTRACT PUBMED 11906285

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

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