2nry: Difference between revisions
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'''Crystal structure of IRAK-4''' | {{Structure | ||
|PDB= 2nry |SIZE=350|CAPTION= <scene name='initialview01'>2nry</scene>, resolution 2.15Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene> | |||
|ACTIVITY= [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] | |||
|GENE= | |||
}} | |||
'''Crystal structure of IRAK-4''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2NRY is a [ | 2NRY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NRY OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17161373 17161373] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
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[[Category: staurosporine]] | [[Category: staurosporine]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:50:18 2008'' | ||
Revision as of 15:50, 20 March 2008
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| 2nry, resolution 2.15Å | |||||||||||||
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| Ligands: | STU | ||||||||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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.
Disease
Known diseases associated with this structure: IRAK4 deficiency OMIM:[606883], Invasive pneumococcal disease, recurrent isolated, 1 OMIM:[606883]
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 Thu Mar 20 17:50:18 2008
