1nq2
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1nq2.jpg|left|200px]] | + | [[Image:1nq2.jpg|left|200px]] |
| - | + | ||
| - | '''Two RTH Mutants with Impaired Hormone Binding''' | + | {{Structure |
| + | |PDB= 1nq2 |SIZE=350|CAPTION= <scene name='initialview01'>1nq2</scene>, resolution 2.4Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=4HY:[4-(4-HYDROXY-3-IODO-PHENOXY)-3,5-DIIODO-PHENYL]-ACETIC+ACID'>4HY</scene> and <scene name='pdbligand=ARS:ARSENIC'>ARS</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= THRB OR NR1A2 OR ERBA2 OR THR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Two RTH Mutants with Impaired Hormone Binding''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1NQ2 is a [ | + | 1NQ2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NQ2 OCA]. |
==Reference== | ==Reference== | ||
| - | Two resistance to thyroid hormone mutants with impaired hormone binding., Huber BR, Sandler B, West BL, Cunha Lima ST, Nguyen HT, Apriletti JW, Baxter JD, Fletterick RJ, Mol Endocrinol. 2003 Apr;17(4):643-52. Epub 2003 Jan 16. PMID:[http:// | + | Two resistance to thyroid hormone mutants with impaired hormone binding., Huber BR, Sandler B, West BL, Cunha Lima ST, Nguyen HT, Apriletti JW, Baxter JD, Fletterick RJ, Mol Endocrinol. 2003 Apr;17(4):643-52. Epub 2003 Jan 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12554782 12554782] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 30: | Line 39: | ||
[[Category: ligand binding domain]] | [[Category: ligand binding domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:00:10 2008'' |
Revision as of 11:00, 20 March 2008
| |||||||
| , resolution 2.4Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | THRB OR NR1A2 OR ERBA2 OR THR1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Two RTH Mutants with Impaired Hormone Binding
Contents |
Overview
Resistance to hormones is commonly due to mutations in genes encoding receptors. Resistance to thyroid hormone is due mostly to mutations of the beta-form of the human (h) thyroid hormone receptor (hTRbeta). We determined x-ray crystal structures of two hTRbeta ligand-binding domains (LBDs), Ala 317 Thr and Arg 316 His. Amino acids 316 and 317 form part of the hormone-binding pocket. The methyl of Ala 317, contacting iodine, sculpts the T3 hormone-binding pocket. Arg 316 is not in direct contact with T3 and has an unknown role in function. Remarkably, the Arg forms part of an unusual buried polar cluster in hTRbeta. Although the identity of the amino acids changes, the polar cluster appears in all nuclear receptors. In spite of the differing roles of 316 and 317, both resistance to thyroid hormone mutants display decreased T3 affinity and weakened transcriptional activation. The two mutants differ in that the Arg 316 His receptor does not form TR-TR homodimers on DNA. 3,5,3'-Triiodothyroacetic acid is bound to both receptors. Thr 317 repositions 3,5,3'-triiodothyroacetic acid distending the face of the receptor that binds coregulators. Arg 316 forms two hydrogen bonds with helix 1. Both are lost with mutation to His displacing helix 1 of the LBD and disordering the loop after helix 1. The stability of the helix 1, deriving in part from the buried polar cluster, is important for hormone binding and formation of TR dimers. The observation that the Arg 316 His mutation affects these functions implies a role for helix 1 in linking hormone binding to the DNA-binding domain-LBD configuration.
Disease
Known diseases associated with this structure: Thyroid hormone resistance OMIM:[190160], Thyroid hormone resistance, autosomal recessive OMIM:[190160]
About this Structure
1NQ2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Two resistance to thyroid hormone mutants with impaired hormone binding., Huber BR, Sandler B, West BL, Cunha Lima ST, Nguyen HT, Apriletti JW, Baxter JD, Fletterick RJ, Mol Endocrinol. 2003 Apr;17(4):643-52. Epub 2003 Jan 16. PMID:12554782
Page seeded by OCA on Thu Mar 20 13:00:10 2008
