PDBsum entry 4olm

Hormone receptor/peptide

PDB id: 4olm

Contents

Protein chain

240 a.a.

Ligands

ASP-SER-ALA-PHE-SER-ARG-TYR-TYR

198

Waters ×13

PDB id:

4olm

Name:

Hormone receptor/peptide

Title:

Crystal structure of w741l-ar-lbd bound with co-regulator peptide

Structure:

Androgen receptor. Chain: a. Fragment: ligand binding doamin. Synonym: dihydrotestosterone receptor, nuclear receptor subfamily 3 group c member 4. Engineered: yes. Mutation: yes. Co-regulator peptide. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ar, dhtr, nr3c4. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes

Resolution:

2.80Å R-factor: 0.256 R-free: 0.313

Authors:

J.S.Liu,C.L.Hsu,W.G.Wu

Key ref:

C.L.Hsu et al. (2014). 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. Mol Oncol, 8, 1575-1587. PubMed id: 25091737 DOI: 10.1016/j.molonc.2014.06.009

Date:

24-Jan-14 Release date: 20-Aug-14

Protein chain

P10275  (ANDR_HUMAN) -  Androgen receptor from Homo sapiens

Seq: 920 a.a.

Struc: 240 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.molonc.2014.06.009

Mol Oncol 8:1575-1587 (2014)

PubMed id: 25091737

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.

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.

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 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.