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2nry

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{{STRUCTURE_2nry| PDB=2nry | SCENE= }}
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'''Crystal structure of IRAK-4'''
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===Crystal structure of IRAK-4===
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==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}}
==About this Structure==
==About this Structure==
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[[Category: Kinase]]
[[Category: Kinase]]
[[Category: Staurosporine]]
[[Category: Staurosporine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:50:10 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:02:03 2008''

Revision as of 12:02, 28 July 2008

Image:2nry.png

Template:STRUCTURE 2nry

Crystal structure of IRAK-4

Template:ABSTRACT PUBMED 17161373

About this Structure

2NRY 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

Page seeded by OCA on Mon Jul 28 15:02:03 2008

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