1yvj

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{{STRUCTURE_1yvj| PDB=1yvj | SCENE= }}
{{STRUCTURE_1yvj| PDB=1yvj | SCENE= }}
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'''Crystal structure of the Jak3 kinase domain in complex with a staurosporine analogue'''
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===Crystal structure of the Jak3 kinase domain in complex with a staurosporine analogue===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15831699 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15831699}}
==Disease==
==Disease==
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[[Category: Stat6]]
[[Category: Stat6]]
[[Category: Tyrosine kinase]]
[[Category: Tyrosine kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:50:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:06:33 2008''

Revision as of 00:06, 28 July 2008

Image:1yvj.png

Template:STRUCTURE 1yvj

Contents

Crystal structure of the Jak3 kinase domain in complex with a staurosporine analogue

Template:ABSTRACT PUBMED 15831699

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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