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| {{STRUCTURE_2nru| PDB=2nru | SCENE= }} | | {{STRUCTURE_2nru| PDB=2nru | SCENE= }} |
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| '''Crystal structure of IRAK-4'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17161373}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17161373 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17161373}} |
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| ==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'' |
