1py5
From Proteopedia
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|PDB= 1py5 |SIZE=350|CAPTION= <scene name='initialview01'>1py5</scene>, resolution 2.3Å | |PDB= 1py5 |SIZE=350|CAPTION= <scene name='initialview01'>1py5</scene>, resolution 2.3Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=PY1:4-(3-PYRIDIN-2-YL-1H-PYRAZOL-4-YL)QUINOLINE'>PY1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= TGFBR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= TGFBR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1pye|1PYE]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1py5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1py5 OCA], [http://www.ebi.ac.uk/pdbsum/1py5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1py5 RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Loeys-Dietz syndrome, type 1A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190181 190181]], Loeys-Dietz syndrome, type 2A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190181 190181]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: Sawyer, J S.]] | [[Category: Sawyer, J S.]] | ||
[[Category: Zhang, F.]] | [[Category: Zhang, F.]] | ||
| - | [[Category: PY1]] | ||
| - | [[Category: SO4]] | ||
[[Category: kinase]] | [[Category: kinase]] | ||
[[Category: receptor i]] | [[Category: receptor i]] | ||
[[Category: tgf-beta]] | [[Category: tgf-beta]] | ||
| - | ''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 23:06:13 2008'' |
Revision as of 20:06, 30 March 2008
| |||||||
| , resolution 2.3Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | TGFBR1 (Homo sapiens) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 1PYE
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of TGF-beta receptor I kinase with inhibitor
Contents |
Overview
We have expanded our previously reported series of pyrazole-based inhibitors of the TGF-beta type I receptor kinase domain (TbetaR-I) to now include new 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole analogues. Limited examination of the SAR of this new series in both enzyme and cell based in vitro assays has revealed selectivity differences with respect to p38 MAP kinase (p38 MAPK) depending on the nature of the 'warhead' group on the dihydropyrrolopyrazole ring. As with our original pyrazole series, phenyl substituents tended to show greater selectivity against p38 MAPK than those comprised of the quinoline-4-yl moiety. We have also achieved co-crystallization and X-ray analysis of compounds 3 and 15, two potent examples of this new series, with the TbetaR-I receptor kinase domain.
Disease
Known disease associated with this structure: Loeys-Dietz syndrome, type 1A OMIM:[190181], Loeys-Dietz syndrome, type 2A OMIM:[190181]
About this Structure
1PY5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain., Sawyer JS, Beight DW, Britt KS, Anderson BD, Campbell RM, Goodson T Jr, Herron DK, Li HY, McMillen WT, Mort N, Parsons S, Smith EC, Wagner JR, Yan L, Zhang F, Yingling JM, Bioorg Med Chem Lett. 2004 Jul 5;14(13):3581-4. PMID:15177479
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