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PDBsum entry 4olm
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Hormone receptor/peptide
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PDB id
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4olm
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References listed in PDB file
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Key reference
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Title
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Identification of a new androgen receptor (ar) co-Regulator bud31 and related peptides to suppress wild-Type and mutated ar-Mediated prostate cancer growth via peptide screening and X-Ray structure analysis.
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Authors
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C.L.Hsu,
J.S.Liu,
P.L.Wu,
H.H.Guan,
Y.L.Chen,
A.C.Lin,
H.J.Ting,
S.T.Pang,
S.D.Yeh,
W.L.Ma,
C.J.Chen,
W.G.Wu,
C.Chang.
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Ref.
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Mol Oncol, 2014,
8,
1575-1587.
[DOI no: ]
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PubMed id
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Abstract
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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
5α-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.
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