1R6G

Crystal structure of the thyroid hormone receptor beta ligand binding domain in complex with a beta selective compound

1R6G の概要

• エントリーDOI: 10.2210/pdb1r6g/pdb
• 分子名称: Thyroid hormone receptor beta-1, 2-[3,5-DIBROMO-4-(4-HYDROXY-3-{HYDROXY[(2-PHENYLETHYL)AMINO]METHYL}PHENOXY)PHENYL]ETHANE-1,1-DIOL (2 entities in total)
• 機能のキーワード: alpha helical, hormone-growth factor receptor complex, hormone/growth factor receptor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P10828
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29826.16

構造登録者

Hangeland, J.J.,Dejneka, T.,Friends, T.J.,Devasthale, P.,Mellstrom, K.,Sandberg, J.,Grynfarb, M.,Doweyko, A.M.,Sack, J.S.,Einspahr, H.,Farnegardh, M.,Husman, B.,Ljunggren, J.,Koehler, K.,Sheppard, C.,Malm, J.,Ryono, D.E. (登録日: 2003-10-15, 公開日: 2005-02-15, 最終更新日: 2024-02-14)

主引用文献

Hangeland, J.J.,Doweyko, A.M.,Dejneka, T.,Friends, T.J.,Devasthale, P.,Mellstrom, K.,Sandberg, J.,Grynfarb, M.,Sack, J.S.,Einspahr, H.,Farnegardh, M.,Husman, B.,Ljunggren, J.,Koehler, K.,Sheppard, C.,Malm, J.,Ryono, D.E.
Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta.
Bioorg.Med.Chem.Lett., 14:3549-3553, 2004

PubMed Abstract: A set of thyromimetics having improved selectivity for TR-beta1 were prepared by replacing the 3'-isopropyl group of 2 and 3 with substituents having increased steric bulk. From this limited SAR study, the most potent and selective compounds identified were derived from 2 and contained a 3'-phenyl moiety bearing small hydrophobic groups meta to the biphenyl link. X-ray crystal data of 15c complexed with TR-beta1 LBD shows methionine 442 to be displaced by the bulky R3' phenyl ethyl amide side chain. Movement of this amino acid side chain provides an expanded pocket for the bulky side chain while the ligand-receptor complex retains full agonist activity.

PubMed: 15177471
DOI: 10.1016/j.bmcl.2004.04.032

実験手法

X-RAY DIFFRACTION (3 Å)