1r6g
From Proteopedia
(New page: 200px<br /> <applet load="1r6g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r6g, resolution 3.00Å" /> '''Crystal structure o...) |
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| - | [[Image:1r6g.gif|left|200px]]<br /> | + | [[Image:1r6g.gif|left|200px]]<br /><applet load="1r6g" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1r6g" size=" | + | |
caption="1r6g, resolution 3.00Å" /> | caption="1r6g, resolution 3.00Å" /> | ||
'''Crystal structure of the thyroid hormone receptor beta ligand binding domain in complex with a beta selective compound'''<br /> | '''Crystal structure of the thyroid hormone receptor beta ligand binding domain in complex with a beta selective compound'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A set of thyromimetics having improved selectivity for TR-beta1 were | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1R6G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 442 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1R6G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=442:'>442</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6G OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Dejneka, T.]] | [[Category: Dejneka, T.]] | ||
[[Category: Devasthale, P.]] | [[Category: Devasthale, P.]] | ||
| - | [[Category: Doweyko, A | + | [[Category: Doweyko, A M.]] |
[[Category: Einspahr, H.]] | [[Category: Einspahr, H.]] | ||
[[Category: Farnegardh, M.]] | [[Category: Farnegardh, M.]] | ||
| - | [[Category: Friends, T | + | [[Category: Friends, T J.]] |
[[Category: Grynfarb, M.]] | [[Category: Grynfarb, M.]] | ||
| - | [[Category: Hangeland, J | + | [[Category: Hangeland, J J.]] |
[[Category: Husman, B.]] | [[Category: Husman, B.]] | ||
[[Category: Koehler, K.]] | [[Category: Koehler, K.]] | ||
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[[Category: Malm, J.]] | [[Category: Malm, J.]] | ||
[[Category: Mellstrom, K.]] | [[Category: Mellstrom, K.]] | ||
| - | [[Category: Ryono, D | + | [[Category: Ryono, D E.]] |
| - | [[Category: Sack, J | + | [[Category: Sack, J S.]] |
[[Category: Sandberg, J.]] | [[Category: Sandberg, J.]] | ||
[[Category: Sheppard, C.]] | [[Category: Sheppard, C.]] | ||
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[[Category: alpha helical]] | [[Category: alpha helical]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:47:34 2008'' |
Revision as of 12:47, 21 February 2008
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Crystal structure of the thyroid hormone receptor beta ligand binding domain in complex with a beta selective compound
Contents |
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.
Disease
Known diseases associated with this structure: Thyroid hormone resistance OMIM:[190160], Thyroid hormone resistance, autosomal recessive OMIM:[190160]
About this Structure
1R6G is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 14:47:34 2008
Categories: Homo sapiens | Single protein | Dejneka, T. | Devasthale, P. | Doweyko, A M. | Einspahr, H. | Farnegardh, M. | Friends, T J. | Grynfarb, M. | Hangeland, J J. | Husman, B. | Koehler, K. | Ljunggren, J. | Malm, J. | Mellstrom, K. | Ryono, D E. | Sack, J S. | Sandberg, J. | Sheppard, C. | 442 | Alpha helical
