Proceedings of the National Academy of Sciences - PNAS, 2001-04, Vol.98 (9), p.4904-4909
2001
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- Autor(en) / Beteiligte
- Titel
- Crystallographic Structures of the Ligand-Binding Domains of the Androgen Receptor and Its T877A Mutant Complexed with the Natural Agonist Dihydrotestosterone
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2001-04, Vol.98 (9), p.4904-4909
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2001
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The structures of the ligand-binding domains (LBD) of the wild-type androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 Å resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface. Binding of the natural ligand dihydrotestosterone by the mutant LBD involves interactions with the same residues as in the wild-type receptor, with the exception of the side chain of threonine 877, which is an alanine residue in the mutant. This structural difference in the binding pocket can explain the ability of the mutant AR found in LNCaP cells (T877A) to accommodate progesterone and other ligands that the wild-type receptor cannot.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.081565498Titel-ID: cdi_pubmed_primary_11320241
- Format
- –
- Schlagworte
- Amino Acid Sequence, Amino Acid Substitution - genetics, Androgens, Animals, Atoms, Binding Sites, Biological Sciences, Crystallography, Crystallography, X-Ray, Dihydrotestosterone - chemistry, Dihydrotestosterone - metabolism, Dihydrotestosterone - pharmacology, Dimerization, Electron density, Genetic mutation, Humans, Ligands, Male, Models, Molecular, Molecular Sequence Data, Molecular structure, Molecules, Mutation, Mutation - genetics, Progesterone - chemistry, Progesterone - metabolism, Prostate cancer, Prostatic Neoplasms - genetics, Protein Structure, Tertiary, Rats, Receptors, Receptors, Androgen - chemistry, Receptors, Androgen - genetics, Receptors, Androgen - metabolism, Receptors, Progesterone - chemistry, Receptors, Progesterone - metabolism, Sequence Alignment, Steroids, Substrate Specificity, Threonine - genetics, Threonine - metabolism, Tumor Cells, Cultured