View source for 4euu


==Structure of BX-795 Complexed with Human TBK1 Kinase Domain Phosphorylated on Ser172==
<StructureSection load='4euu' size='340' side='right'caption='[[4euu]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4euu]] is a 2 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=4EUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUU 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BX7:N-(3-{[5-IODO-4-({3-[(THIOPHEN-2-YLCARBONYL)AMINO]PROPYL}AMINO)PYRIMIDIN-2-YL]AMINO}PHENYL)PYRROLIDINE-1-CARBOXAMIDE'>BX7</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4euu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4euu OCA], [https://pdbe.org/4euu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4euu RCSB], [https://www.ebi.ac.uk/pdbsum/4euu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4euu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TBK1_HUMAN TBK1_HUMAN] Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFN-alpha and IFN-beta. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS or SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates and activates AKT1. Phosphorylates Borna disease virus (BDV) P protein.<ref>PMID:10581243</ref> <ref>PMID:10783893</ref> <ref>PMID:11839743</ref> <ref>PMID:12692549</ref> <ref>PMID:12702806</ref> <ref>PMID:14703513</ref> <ref>PMID:15485837</ref> <ref>PMID:15489227</ref> <ref>PMID:15367631</ref> <ref>PMID:18583960</ref> <ref>PMID:21270402</ref> <ref>PMID:21464307</ref> <ref>PMID:21617041</ref> <ref>PMID:21138416</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tank-binding kinase (TBK)1 plays a central role in innate immunity: it serves as an integrator of multiple signals induced by receptor-mediated pathogen detection and as a modulator of IFN levels. Efforts to better understand the biology of this key immunological factor have intensified recently as growing evidence implicates aberrant TBK1 activity in a variety of autoimmune diseases and cancers. Nevertheless, key molecular details of TBK1 regulation and substrate selection remain unanswered. Here, structures of phosphorylated and unphosphorylated human TBK1 kinase and ubiquitin-like domains, combined with biochemical studies, indicate a molecular mechanism of activation via transautophosphorylation. These TBK1 structures are consistent with the tripartite architecture observed recently for the related kinase IKKbeta, but domain contributions toward target recognition appear to differ for the two enzymes. In particular, both TBK1 autoactivation and substrate specificity are likely driven by signal-dependent colocalization events.

Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation.,Ma X, Helgason E, Phung QT, Quan CL, Iyer RS, Lee MW, Bowman KK, Starovasnik MA, Dueber EC Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9378-83. Epub 2012 May 22. PMID:22619329<ref>PMID:22619329</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4euu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bowman KK]]
[[Category: Dueber EC]]
[[Category: Helgason E]]
[[Category: Iyer RS]]
[[Category: Lee MW]]
[[Category: Ma X]]
[[Category: Phung QT]]
[[Category: Quan CL]]
[[Category: Starovasnik MA]]