1gs4
From Proteopedia
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| - | [[Image:1gs4.gif|left|200px]]<br /> | + | [[Image:1gs4.gif|left|200px]]<br /><applet load="1gs4" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1gs4" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="1gs4, resolution 1.95Å" /> | caption="1gs4, resolution 1.95Å" /> | ||
'''STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER'''<br /> | '''STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1GS4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 and ZK5 as [http://en.wikipedia.org/wiki/ligands ligands]. | + | 1GS4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 and ZK5 as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:Po4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GS4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: prostate cancer]] | [[Category: prostate cancer]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 15:34:01 2007'' |
Revision as of 13:24, 18 December 2007
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STRUCTURAL BASIS FOR THE GLUCOCORTICOID RESPONSE IN A MUTANT HUMAN ANDROGEN RECEPTOR (ARCCR) DERIVED FROM AN ANDROGEN-INDEPENDENT PROSTATE CANCER
Contents |
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.
Disease
Known diseases associated with this structure: Androgen insensitivity OMIM:[313700], Breast cancer, male, with Reifenstein syndrome OMIM:[313700], Hypospadias, perineal OMIM:[313700], Prostate cancer OMIM:[313700], Prostate cancer, susceptibility to OMIM:[313700], Spinal and bulbar muscular atrophy of Kennedy OMIM:[313700]
About this Structure
1GS4 is a Single protein structure of sequence from Homo sapiens with PO4 and ZK5 as ligands. Known structural/functional Site: . 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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