1py5
From Proteopedia
(New page: 200px<br /> <applet load="1py5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1py5, resolution 2.3Å" /> '''Crystal Structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1py5.gif|left|200px]]<br /> | + | [[Image:1py5.gif|left|200px]]<br /><applet load="1py5" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1py5" size=" | + | |
caption="1py5, resolution 2.3Å" /> | caption="1py5, resolution 2.3Å" /> | ||
'''Crystal Structure of TGF-beta receptor I kinase with inhibitor'''<br /> | '''Crystal Structure of TGF-beta receptor I kinase with inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have expanded our previously reported series of pyrazole-based | + | 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== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1PY5 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 SO4 and PY1 as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1PY5 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=SO4:'>SO4</scene> and <scene name='pdbligand=PY1:'>PY1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1PY5 OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Sawyer, J | + | [[Category: Sawyer, J S.]] |
[[Category: Zhang, F.]] | [[Category: Zhang, F.]] | ||
[[Category: PY1]] | [[Category: PY1]] | ||
| Line 26: | Line 25: | ||
[[Category: tgf-beta]] | [[Category: tgf-beta]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:33:47 2008'' |
Revision as of 12:33, 21 February 2008
|
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 diseases associated with this structure: Aortic aneurysm, familial thoracic 5 OMIM:[190181], Furlong syndrome OMIM:[190181], Loeys-Dietz syndrome OMIM:[190181]
About this Structure
1PY5 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 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
Page seeded by OCA on Thu Feb 21 14:33:47 2008
