2nru: Difference between revisions
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|PDB= 2nru |SIZE=350|CAPTION= <scene name='initialview01'>2nru</scene>, resolution 2.00Å | |PDB= 2nru |SIZE=350|CAPTION= <scene name='initialview01'>2nru</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | |LIGAND= <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=T12:1-(3-HYDROXYPROPYL)-2-[(3-NITROBENZOYL)AMINO]-1H-BENZIMIDAZOL-5-YL+PIVALATE'>T12</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= IRAK4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= IRAK4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2nry|2NRY]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nru OCA], [http://www.ebi.ac.uk/pdbsum/2nru PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2nru RCSB]</span> | |||
}} | }} | ||
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==Disease== | ==Disease== | ||
Known | Known disease associated with this structure: IRAK4 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606883 606883]], Invasive pneumococcal disease, recurrent isolated, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606883 606883]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Walker, N P.C.]] | [[Category: Walker, N P.C.]] | ||
[[Category: Wang, Z.]] | [[Category: Wang, Z.]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
[[Category: irak]] | [[Category: irak]] | ||
[[Category: kinase]] | [[Category: kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:07:24 2008'' | ||
Revision as of 01:07, 31 March 2008
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| 2nru, resolution 2.00Å | |||||||||||||
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| Ligands: | SEP, SO4, T12, TPO | ||||||||||||
| Gene: | IRAK4 (Homo sapiens) | ||||||||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||||||||
| Related: | 2NRY
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| 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 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
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