2nry
From Proteopedia
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Crystal structure of IRAK-4
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.
About this Structure
2NRY is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 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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