1vjy
From Proteopedia
(New page: 200px<br /> <applet load="1vjy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vjy, resolution 2.0Å" /> '''Crystal Structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1vjy.gif|left|200px]]<br /> | + | [[Image:1vjy.gif|left|200px]]<br /><applet load="1vjy" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1vjy" size=" | + | |
caption="1vjy, resolution 2.0Å" /> | caption="1vjy, resolution 2.0Å" /> | ||
'''Crystal Structure of a Naphthyridine Inhibitor of Human TGF-beta Type I Receptor'''<br /> | '''Crystal Structure of a Naphthyridine Inhibitor of Human TGF-beta Type I Receptor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Optimization of the screening hit 1 led to the identification of novel | + | Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1VJY 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 460 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | + | 1VJY 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=460:'>460</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VJY OCA]. |
==Reference== | ==Reference== | ||
| Line 19: | Line 18: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Boullay, V.]] | [[Category: Boullay, V.]] | ||
| - | [[Category: Fouchet, M | + | [[Category: Fouchet, M H.]] |
[[Category: Gellibert, F.]] | [[Category: Gellibert, F.]] | ||
[[Category: Goodland, H.]] | [[Category: Goodland, H.]] | ||
| - | [[Category: Gouville, A | + | [[Category: Gouville, A C.de.]] |
[[Category: Hartley, D.]] | [[Category: Hartley, D.]] | ||
[[Category: Huet, S.]] | [[Category: Huet, S.]] | ||
| Line 30: | Line 29: | ||
[[Category: Lovegrove, V.]] | [[Category: Lovegrove, V.]] | ||
[[Category: Mathews, N.]] | [[Category: Mathews, N.]] | ||
| - | [[Category: Nguyen, V | + | [[Category: Nguyen, V L.]] |
[[Category: Sautet, S.]] | [[Category: Sautet, S.]] | ||
[[Category: Smith, W.]] | [[Category: Smith, W.]] | ||
| Line 40: | Line 39: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:36:07 2008'' |
Revision as of 13:36, 21 February 2008
|
Crystal Structure of a Naphthyridine Inhibitor of Human TGF-beta Type I Receptor
Contents |
Overview
Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies.
Disease
Known diseases associated with this structure: Aortic aneurysm, familial thoracic 5 OMIM:[190181], Furlong syndrome OMIM:[190181], Loeys-Dietz syndrome OMIM:[190181]
About this Structure
1VJY is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors., Gellibert F, Woolven J, Fouchet MH, Mathews N, Goodland H, Lovegrove V, Laroze A, Nguyen VL, Sautet S, Wang R, Janson C, Smith W, Krysa G, Boullay V, De Gouville AC, Huet S, Hartley D, J Med Chem. 2004 Aug 26;47(18):4494-506. PMID:15317461
Page seeded by OCA on Thu Feb 21 15:36:07 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Boullay, V. | Fouchet, M H. | Gellibert, F. | Goodland, H. | Gouville, A C.de. | Hartley, D. | Huet, S. | Janson, C. | Krysa, G. | Laroze, A. | Lovegrove, V. | Mathews, N. | Nguyen, V L. | Sautet, S. | Smith, W. | Wang, R. | Woolven, J. | 460 | Inhibitor complex | Protein kinase | Transferase
