6ti8: Difference between revisions

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<StructureSection load='6ti8' size='340' side='right'caption='[[6ti8]], [[Resolution|resolution]] 2.32&Aring;' scene=''>
<StructureSection load='6ti8' size='340' side='right'caption='[[6ti8]], [[Resolution|resolution]] 2.32&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ti8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TI8 FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TI8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.32&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.32&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NBW:~{N},~{N}-dimethyl-4-(1-methylcyclopropyl)oxy-2-[[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]amino]pyrido[3,2-d]pyrimidine-6-carboxamide'>NBW</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NBW:~{N},~{N}-dimethyl-4-(1-methylcyclopropyl)oxy-2-[[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]amino]pyrido[3,2-d]pyrimidine-6-carboxamide'>NBW</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ti8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ti8 OCA], [https://pdbe.org/6ti8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ti8 RCSB], [https://www.ebi.ac.uk/pdbsum/6ti8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ti8 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ti8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ti8 OCA], [https://pdbe.org/6ti8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ti8 RCSB], [https://www.ebi.ac.uk/pdbsum/6ti8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ti8 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IRAK4_HUMAN IRAK4_HUMAN] Defects in IRAK4 are the cause of recurrent isolated invasive pneumococcal disease type 1 (IPD1) [MIM:[https://omim.org/entry/610799 610799]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref>  Defects in IRAK4 are the cause of IRAK4 deficiency (IRAK4D) [MIM:[https://omim.org/entry/607676 607676]. IRAK4 deficiency causes extracellular pyogenic bacterial and fungal infections in otherwise healthy children.<ref>PMID:12925671</ref> <ref>PMID:12637671</ref>
== Function ==
[https://www.uniprot.org/uniprot/IRAK4_HUMAN IRAK4_HUMAN] Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections.<ref>PMID:11960013</ref> <ref>PMID:12538665</ref> <ref>PMID:15084582</ref> <ref>PMID:17217339</ref> <ref>PMID:17337443</ref> <ref>PMID:17997719</ref> <ref>PMID:20400509</ref>


==See Also==
==See Also==
*[[Interleukin-1 receptor-associated kinase|Interleukin-1 receptor-associated kinase]]
*[[Interleukin-1 receptor-associated kinase|Interleukin-1 receptor-associated kinase]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Aagaard A]]
[[Category: Aagaard A]]
[[Category: Degorce SL]]
[[Category: Degorce SL]]
[[Category: Xue Y]]
[[Category: Xue Y]]

Latest revision as of 13:30, 23 October 2024

IRAK4 IN COMPLEX WITH inhibitorIRAK4 IN COMPLEX WITH inhibitor

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.32Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

See Also

6ti8, resolution 2.32Å

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