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2nru
From Proteopedia
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'''Crystal structure of IRAK-4''' | '''Crystal structure of IRAK-4''' | ||
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[[Category: Walker, N P.C.]] | [[Category: Walker, N P.C.]] | ||
[[Category: Wang, Z.]] | [[Category: Wang, Z.]] | ||
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| - | [[Category: | + | [[Category: Irak]] |
| - | [[Category: | + | [[Category: Kinase]] |
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Revision as of 06:50, 4 May 2008
Crystal structure of IRAK-4
Contents |
Overview
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.
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 Page seeded by OCA on Sun May 4 09:50:00 2008
