4ztl: Difference between revisions

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<StructureSection load='4ztl' size='340' side='right'caption='[[4ztl]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
<StructureSection load='4ztl' size='340' side='right'caption='[[4ztl]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ztl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZTL FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ztl]] 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=4ZTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZTL FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4S1:(1R,2S,3R,5R)-3-{[5-(1,3-BENZOTHIAZOL-2-YL)-2-(PROPYLAMINO)PYRIMIDIN-4-YL]AMINO}-5-(HYDROXYMETHYL)CYCLOPENTANE-1,2-DIOL'>4S1</scene></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]] 2.39&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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=4S1:(1R,2S,3R,5R)-3-{[5-(1,3-BENZOTHIAZOL-2-YL)-2-(PROPYLAMINO)PYRIMIDIN-4-YL]AMINO}-5-(HYDROXYMETHYL)CYCLOPENTANE-1,2-DIOL'>4S1</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ztm|4ztm]], [[4ztn|4ztn]]</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=4ztl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ztl OCA], [https://pdbe.org/4ztl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ztl RCSB], [https://www.ebi.ac.uk/pdbsum/4ztl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ztl ProSAT]</span></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IRAK4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ztl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ztl OCA], [http://pdbe.org/4ztl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ztl RCSB], [http://www.ebi.ac.uk/pdbsum/4ztl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ztl ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/IRAK4_HUMAN IRAK4_HUMAN]] Defects in IRAK4 are the cause of recurrent isolated invasive pneumococcal disease type 1 (IPD1) [MIM:[http://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:[http://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>
[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 ==
== Function ==
[[http://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>
[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>  
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Fischmann TO]]
[[Category: Fischmann, T O]]
[[Category: Kinase]]
[[Category: Phosphatase]]
[[Category: Transferase-transferase inhibitor complex]]

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