1R6G

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

Summary for 1R6G

• Entry DOI: 10.2210/pdb1r6g/pdb
• Descriptor: 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)
• Functional Keywords: alpha helical, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P10828
• Total number of polymer chains: 1
• Total formula weight: 29826.16

Authors

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. (deposition date: 2003-10-15, release date: 2005-02-15, Last modification date: 2024-02-14)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3 Å)