CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN T877A MUTANT COMPLEX WITH DIHYDROTESTOSTERONE

File:1i38.gif


1i38, resolution 2.00Å

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OverviewOverview

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.

About this StructureAbout this Structure

1I38 is a Single protein structure of sequence from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone., Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR Jr, Weinmann R, Einspahr HM, Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4904-9. PMID:11320241

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