3B65

Crystal structure of the androgen receptor ligand binding domain in complex with SARM S-24

3B65 の概要

• エントリーDOI: 10.2210/pdb3b65/pdb
• 関連するPDBエントリー: 2axa 3B5R 3B66 3B67 3B68
• 分子名称: Androgen receptor, (2S)-N-(4-cyano-3-iodophenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide (3 entities in total)
• 機能のキーワード: androgen receptor, sarm, disease mutation, dna-binding, lipid-binding, metal-binding, nucleus, polymorphism, steroid-binding, transcription, transcription regulation, triplet repeat expansion, ubl conjugation, zinc, zinc-finger
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P10275
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29493.30

構造登録者

Bohl, C.E.,Miller, D.D.,Dalton, J.T. (登録日: 2007-10-27, 公開日: 2008-09-09, 最終更新日: 2024-02-21)

主引用文献

Bohl, C.E.,Wu, Z.,Chen, J.,Mohler, M.L.,Yang, J.,Hwang, D.J.,Mustafa, S.,Miller, D.D.,Bell, C.E.,Dalton, J.T.
Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators
Bioorg.Med.Chem.Lett., 18:5567-5570, 2008

PubMed Abstract: Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to as the B-ring. We found that hydrophilic B-ring para-substituted analogs exhibit an additional region of hydrogen bonding not seen with steroidal compounds and that multiple halogen substitutions affect the B-ring conformation and aromatic interactions with Trp741. This information elucidates interactions important for high AR binding affinity and provides new insight for structure-based drug design.

PubMed: 18805694
DOI: 10.1016/j.bmcl.2008.09.002

実験手法

X-RAY DIFFRACTION (1.8 Å)