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PDBsum entry 1i37
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Hormone/growth factor
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PDB id
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1i37
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystallographic structures of the ligand-Binding domains of the androgen receptor and its t877a mutant complexed with the natural agonist dihydrotestosterone.
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Authors
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J.S.Sack,
K.F.Kish,
C.Wang,
R.M.Attar,
S.E.Kiefer,
Y.An,
G.Y.Wu,
J.E.Scheffler,
M.E.Salvati,
S.R.Krystek,
R.Weinmann,
H.M.Einspahr.
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Ref.
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Proc Natl Acad Sci U S A, 2001,
98,
4904-4909.
[DOI no: ]
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PubMed id
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Abstract
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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 A 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.
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Figure 1.
Fig. 1. Chemical structures of DHT and progesterone.
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Figure 4.
Fig. 4. Ribbon-style drawing of the AR LBD. The substrate
DHT and the side chains that interact with it are shown as
ball-and-stick figures. Figs. 5, 6, and 8 were drawn by using
ICM Ver. 2.
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