1yvj
From Proteopedia
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| - | [[Image:1yvj.gif|left|200px]] | + | [[Image:1yvj.gif|left|200px]] |
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| - | '''Crystal structure of the Jak3 kinase domain in complex with a staurosporine analogue''' | + | {{Structure |
| + | |PDB= 1yvj |SIZE=350|CAPTION= <scene name='initialview01'>1yvj</scene>, resolution 2.55Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</scene> and <scene name='pdbligand=4ST:1,2,3,4-TETRAHYDROGEN-STAUROSPORINE'>4ST</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] | ||
| + | |GENE= JAK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of the Jak3 kinase domain in complex with a staurosporine analogue''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YVJ is a [ | + | 1YVJ 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=1YVJ OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog., Boggon TJ, Li Y, Manley PW, Eck MJ, Blood. 2005 Aug 1;106(3):996-1002. Epub 2005 Apr 14. PMID:[http:// | + | Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog., Boggon TJ, Li Y, Manley PW, Eck MJ, Blood. 2005 Aug 1;106(3):996-1002. Epub 2005 Apr 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15831699 15831699] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: tyrosine kinase; scid; severe combined immunodeficiency; stat5; stat6; interleukin-2; common-gamma chain]] | [[Category: tyrosine kinase; scid; severe combined immunodeficiency; stat5; stat6; interleukin-2; common-gamma chain]] | ||
| - | ''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 15:28:02 2008'' |
Revision as of 13:28, 20 March 2008
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| , resolution 2.55Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | JAK3 (Homo sapiens) | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the Jak3 kinase domain in complex with a staurosporine analogue
Contents |
Overview
Jak (Janus kinase) family nonreceptor tyrosine kinases are central mediators of cytokine signaling. The Jak kinases exhibit distinct cytokine receptor association profiles and so transduce different signals. Jak3 expression is limited to the immune system, where it plays a key role in signal transduction from cytokine receptors containing the common gamma-chain, gammac. Patients unable to signal via gammac present with severe combined immunodeficiency (SCID). The finding that Jak3 mutations result in SCID has made it a target for development of lymphocyte-specific immunosuppressants. Here, we present the crystal structure of the Jak3 kinase domain in complex with staurosporine analog AFN941. The kinase domain is in the active conformation, with both activation loop tyrosine residues phosphorylated. The phosphate group on pTyr981 in the activation loop is in part coordinated by an arginine residue in the regulatory C-helix, suggesting a direct mechanism by which the active position of the C-helix is induced by phosphorylation of the activation loop. Such a direct coupling has not been previously observed in tyrosine kinases and may be unique to Jak kinases. The crystal structure provides a detailed view of the Jak3 active site and will facilitate computational and structure-directed approaches to development of Jak3-specific inhibitors.
Disease
Known disease associated with this structure: SCID, autosomal recessive, T-negative/B-positive type OMIM:[600173]
About this Structure
1YVJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog., Boggon TJ, Li Y, Manley PW, Eck MJ, Blood. 2005 Aug 1;106(3):996-1002. Epub 2005 Apr 14. PMID:15831699
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