1z95: Difference between revisions
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|PDB= 1z95 |SIZE=350|CAPTION= <scene name='initialview01'>1z95</scene>, resolution 1.80Å | |PDB= 1z95 |SIZE=350|CAPTION= <scene name='initialview01'>1z95</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=198:R-BICALUTAMIDE'>198</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z95 OCA], [http://www.ebi.ac.uk/pdbsum/1z95 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1z95 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Carcinoma of the prostate is the most commonly diagnosed cancer in men. The current pharmacological treatment of choice for progressive androgen-dependent prostate cancer is the nonsteroidal antiandrogen, bicalutamide, either as monotherapy or with adjuvant castration or luteinizing hormone-releasing hormone superagonists to block the synthesis of endogenous testosterone. To date, no nonsteroidal or antagonist-bound androgen receptor (AR) structure is available. We solved the x-ray crystal structure of the mutant W741L AR ligand-binding domain bound to R-bicalutamide at 1.8-A resolution. This mutation confers agonist activity to bicalutamide and is likely involved in bicalutamide withdrawal syndrome. The three-dimensional structure demonstrates that the B ring of R-bicalutamide in the W741L mutant is accommodated at the location of the indole ring of Trp-741 in the WT AR bound to dihydrotestosterone. Knowledge of the binding mechanism for R-bicalutamide will provide molecular rationale for the development of new antiandrogens and selective AR modulators. | Carcinoma of the prostate is the most commonly diagnosed cancer in men. The current pharmacological treatment of choice for progressive androgen-dependent prostate cancer is the nonsteroidal antiandrogen, bicalutamide, either as monotherapy or with adjuvant castration or luteinizing hormone-releasing hormone superagonists to block the synthesis of endogenous testosterone. To date, no nonsteroidal or antagonist-bound androgen receptor (AR) structure is available. We solved the x-ray crystal structure of the mutant W741L AR ligand-binding domain bound to R-bicalutamide at 1.8-A resolution. This mutation confers agonist activity to bicalutamide and is likely involved in bicalutamide withdrawal syndrome. The three-dimensional structure demonstrates that the B ring of R-bicalutamide in the W741L mutant is accommodated at the location of the indole ring of Trp-741 in the WT AR bound to dihydrotestosterone. Knowledge of the binding mechanism for R-bicalutamide will provide molecular rationale for the development of new antiandrogens and selective AR modulators. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Gao, W.]] | [[Category: Gao, W.]] | ||
[[Category: Miller, D D.]] | [[Category: Miller, D D.]] | ||
[[Category: | [[Category: cellular differentiation]] | ||
[[Category: | [[Category: cellular proliferation]] | ||
[[Category: steroid | [[Category: receptor]] | ||
[[Category: steroid hormone]] | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:32:26 2008'' | ||
