2nru: Difference between revisions
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New page: left|200px<br /> <applet load="2nru" size="450" color="white" frame="true" align="right" spinBox="true" caption="2nru, resolution 2.00Å" /> '''Crystal structure o... |
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[[Image:2nru. | [[Image:2nru.jpg|left|200px]]<br /><applet load="2nru" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2nru" size=" | |||
caption="2nru, resolution 2.00Å" /> | caption="2nru, resolution 2.00Å" /> | ||
'''Crystal structure of IRAK-4'''<br /> | '''Crystal structure of IRAK-4'''<br /> | ||
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==Overview== | ==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. | 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== | ==About this Structure== | ||
2NRU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and T12 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | 2NRU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=T12:'>T12</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NRU OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: kinase]] | [[Category: kinase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:24:24 2008'' | ||
