4OKT: Crystal Structure Of W741l-ar-lbd Bound With Co-regulator Peptide

Citation:
Abstract
Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5alpha-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.
PDB ID: 4OKTDownload
MMDB ID: 122547
PDB Deposition Date: 2014/1/22
Updated in MMDB: 2014/08
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4OKT: dimeric; determined by author and by software (PISA)
Molecular Components in 4OKT
Label Count Molecule
Proteins (2 molecules)
1
Androgen Receptor(Gene symbol: AR)
Molecule annotation
1
Co-regulator Peptide
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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