1r6g: Difference between revisions
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= THRB, NR1A2, ERBA2, THR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= THRB, NR1A2, ERBA2, THR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1r6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6g OCA], [http://www.ebi.ac.uk/pdbsum/1r6g PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1r6g RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sandberg, J.]] | [[Category: Sandberg, J.]] | ||
[[Category: Sheppard, C.]] | [[Category: Sheppard, C.]] | ||
[[Category: alpha helical]] | [[Category: alpha helical]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:23:54 2008'' | ||
Revision as of 23:23, 30 March 2008
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| , resolution 3.00Å | |||||||
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| Ligands: | |||||||
| Gene: | THRB, NR1A2, ERBA2, THR1 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the thyroid hormone receptor beta ligand binding domain in complex with a beta selective compound
OverviewOverview
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.
About this StructureAbout this Structure
1R6G is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta., Hangeland JJ, Doweyko AM, Dejneka T, Friends TJ, Devasthale P, Mellstrom K, Sandberg J, Grynfarb M, Sack JS, Einspahr H, Farnegardh M, Husman B, Ljunggren J, Koehler K, Sheppard C, Malm J, Ryono DE, Bioorg Med Chem Lett. 2004 Jul 5;14(13):3549-53. PMID:15177471
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