2nru: Difference between revisions

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[[Image:2nru.jpg|left|200px]]
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[[Image:2nru.png|left|200px]]


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{{STRUCTURE_2nru|  PDB=2nru  |  SCENE=  }}  
{{STRUCTURE_2nru|  PDB=2nru  |  SCENE=  }}  


'''Crystal structure of IRAK-4'''
===Crystal structure of IRAK-4===




==Overview==
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Interleukin-1 (IL-1) receptor-associated kinase-4 (IRAK-4) is a serine/threonine kinase that plays an essential role in signal transduction by Toll/IL-1 receptors (TIRs). Here, we report the crystal structures of the phosphorylated human IRAK-4 kinase domain in complex with a potent inhibitor and with staurosporine to 2.0 and 2.2 A, respectively. The structures reveal that IRAK-4 has a unique tyrosine gatekeeper residue that interacts with the conserved glutamate from helix alphaC. Consequently, helix alphaC is "pulled in" to maintain the active orientation, and the usual pre-existing hydrophobic back pocket of the ATP-binding site is abolished. The peptide substrate-binding site is more open when compared with other protein kinases due to a marked movement of helix alphaG. The pattern of phosphate ligand interactions in the activation loop bears a close resemblance to that of a tyrosine kinase. Our results provide insights into IRAK-4 function and the design of selective inhibitors.
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{{ABSTRACT_PUBMED_17161373}}


==Disease==
==Disease==
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[[Category: Irak]]
[[Category: Irak]]
[[Category: Kinase]]
[[Category: Kinase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 09:50:00 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:26:26 2008''

Revision as of 13:26, 27 July 2008

File:2nru.png

Template:STRUCTURE 2nru

Crystal structure of IRAK-4

Template:ABSTRACT PUBMED 17161373

Disease

Known disease associated with this structure: IRAK4 deficiency OMIM:[606883], Invasive pneumococcal disease, recurrent isolated, 1 OMIM:[606883]

About this Structure

2NRU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structures of IRAK-4 kinase in complex with inhibitors: a serine/threonine kinase with tyrosine as a gatekeeper., Wang Z, Liu J, Sudom A, Ayres M, Li S, Wesche H, Powers JP, Walker NP, Structure. 2006 Dec;14(12):1835-44. PMID:17161373

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