1N46

CRYSTAL STRUCTURE OF HUMAN TR BETA LIGAND-BINDING DOMAIN COMPLEXED WITH A POTENT SUBTYPE-SELECTIVE THYROMIMETIC

Summary for 1N46

• Entry DOI: 10.2210/pdb1n46/pdb
• Descriptor: Thyroid hormone receptor Beta-1, [4-(4-HYDROXY-3-ISOPROPYL-PHENOXY)-3,5-DIMETHYL-PHENYL]-6-AZAURACIL (3 entities in total)
• Functional Keywords: transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P10828
• Total number of polymer chains: 2
• Total formula weight: 59040.34

Authors

Dow, R.L.,Schneider, S.R.,Paight, E.S.,Hank, R.F.,Chiang, P.,Cornelius, P.,Lee, E.,Newsome, W.P.,Swick, A.G.,Spitzer, J.,Hargrove, D.M.,Patterson, T.A.,Pandit, J.,Chrunyk, B.A.,LeMotte, P.K.,Danley, D.E.,Rosner, M.H.,Ammirati, M.J.,Simons, S.P.,Schulte, G.K.,Tate, B.F.,DaSilva-Jardine, P. (deposition date: 2002-10-30, release date: 2003-04-22, Last modification date: 2024-02-14)

Primary citation

Dow, R.L.,Schneider, S.R.,Paight, E.S.,Hank, R.F.,Chiang, P.,Cornelius, P.,Lee, E.,Newsome, W.P.,Swick, A.G.,Spitzer, J.,Hargrove, D.M.,Patterson, T.A.,Pandit, J.,Chrunyk, B.A.,LeMotte, P.K.,Danley, D.E.,Rosner, M.H.,Ammirati, M.J.,Simons, S.P.,Schulte, G.K.,Tate, B.F.,DaSilva-Jardine, P.
Discovery of a Novel Series of 6-Azauracil-Based Thyroid Hormone Receptor Ligands: Potent, TRbeta Subtype-Selective Thyromimetics
Bioorg.Med.Chem.Lett., 13:379-382, 2003

PubMed Abstract: In this communication, we wish to describe the discovery of a novel series of 6-azauracil-based thyromimetics that possess up to 100-fold selectivities for binding and functional activation of the beta(1)-isoform of the thyroid receptor family. Structure-activity relationship studies on the 3,5- and 3'-positions provided compounds with enhanced TR beta affinity and selectivity. Key binding interactions between the 6-azauracil moiety and the receptor have been determined through of X-ray crystallographic analysis.

PubMed: 12565933
DOI: 10.1016/S0960-894X(02)00947-2

Experimental method

X-RAY DIFFRACTION (2.2 Å)