4eut - Revision history

OCA at 11:06, 1 March 2024

2024-03-01T11:06:10Z

← Older revision		Revision as of 11:06, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eut]] 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUT FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eut]] 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUT FirstGlance]. <br>
	</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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.6Å</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=IOD:IODIDE+ION'>IOD</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=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [https://pdbe.org/4eut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [https://www.ebi.ac.uk/pdbsum/4eut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eut 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=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [https://pdbe.org/4eut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [https://www.ebi.ac.uk/pdbsum/4eut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eut ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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>		[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®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4eut" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==

OCA at 04:17, 7 October 2022

2022-10-07T04:17:30Z

← Older revision		Revision as of 04:17, 7 October 2022
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	==Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain==		==Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain==
	<StructureSection load='4eut' size='340' side='right' caption='[[4eut]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4eut' size='340' side='right'caption='[[4eut]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eut]] is a 2 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EUT FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eut]] 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~		</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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4euu\|4euu]]</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=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [https://pdbe.org/4eut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [https://www.ebi.ac.uk/pdbsum/4eut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eut ProSAT]</span></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TBK1, NAK ([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=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [~~http~~://pdbe.org/4eut PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4eut PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4eut ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://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>		[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4eut" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4eut" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Non-specific serine/threonine protein kinase~~]]		[[Category: Large Structures]]
	[[Category: Bowman~~, K K~~]]		[[Category: Bowman KK]]
	[[Category: Dueber~~, E C~~]]		[[Category: Dueber EC]]
	[[Category: Helgason, E]]		[[Category: Helgason E]]
	[[Category: Iyer~~, R S~~]]		[[Category: Iyer RS]]
	[[Category: Lee~~, M W~~]]		[[Category: Lee MW]]
	[[Category: Ma, X]]		[[Category: Ma X]]
	[[Category: Phung~~, Q T~~]]		[[Category: Phung QT]]
	[[Category: Quan~~, C L~~]]		[[Category: Quan CL]]
	[[Category: Starovasnik~~, M A]]~~		[[Category: Starovasnik MA]]
	~~[[Category: Atp binding]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Phosphorylation]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 08:10, 15 November 2017

2017-11-15T08:10:06Z

← Older revision		Revision as of 08:10, 15 November 2017
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	</div>		</div>
	<div class="pdbe-citations 4eut" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4eut" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 23:53, 4 August 2016

2016-08-04T23:53:16Z

← Older revision		Revision as of 23:53, 4 August 2016
Line 1:		Line 1:

	==Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain==		==Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain==
	<StructureSection load='4eut' size='340' side='right' caption='[[4eut]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4eut' size='340' side='right' caption='[[4eut]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eut]] is a 2 chain structure with 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUT FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eut]] is a 2 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4euu\|4euu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4euu\|4euu]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TBK1, NAK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TBK1, NAK ([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='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=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [http://www.ebi.ac.uk/pdbsum/4eut PDBsum]</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=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [http://pdbe.org/4eut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [http://www.ebi.ac.uk/pdbsum/4eut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eut ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4eut" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bowman, K K]]		[[Category: Bowman, K K]]

OCA at 14:09, 25 December 2014

2014-12-25T14:09:35Z

← Older revision		Revision as of 14:09, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eut]] is a 2 chain structure with 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUT FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eut]] is a 2 chain structure with 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUT FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4euu\|4euu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4euu\|4euu]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TBK1, NAK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TBK1, NAK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [http://www.ebi.ac.uk/pdbsum/4eut PDBsum]</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=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [http://www.ebi.ac.uk/pdbsum/4eut PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 28:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bowman, K K.]]		[[Category: Bowman, K K]]
	[[Category: Dueber, E C.]]		[[Category: Dueber, E C]]
	[[Category: Helgason, E.]]		[[Category: Helgason, E]]
	[[Category: Iyer, R S.]]		[[Category: Iyer, R S]]
	[[Category: Lee, M W.]]		[[Category: Lee, M W]]
	[[Category: Ma, X.]]		[[Category: Ma, X]]
	[[Category: Phung, Q T.]]		[[Category: Phung, Q T]]
	[[Category: Quan, C L.]]		[[Category: Quan, C L]]
	[[Category: Starovasnik, M A.]]		[[Category: Starovasnik, M A]]
	[[Category: Atp binding]]		[[Category: Atp binding]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Phosphorylation]]		[[Category: Phosphorylation]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:07, 11 June 2014

2014-06-11T09:07:10Z

← Older revision		Revision as of 09:07, 11 June 2014
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	[[~~Image~~:~~4eut~~.~~png~~\|~~left~~\|~~200px~~]]		==Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain==
			<StructureSection load='4eut' size='340' side='right' caption='[[4eut]], [[Resolution\|resolution]] 2.60Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4eut]] is a 2 chain structure with 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=4EUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUT FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4euu\|4euu]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TBK1, NAK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eut OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eut RCSB], [http://www.ebi.ac.uk/pdbsum/4eut PDBsum]</span></td></tr>
			<table>
			<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.

	~~{{STRUCTURE_4eut\| PDB=4eut \| SCENE= }}~~		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>

	~~===Structure~~ of ~~BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_22619329}}~~		==See Also==
			*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	==~~About this Structure~~==		== References ==
	[[~~4eut]] is a 2 chain structure with 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=4EUT OCA~~].		<references/>
			__TOC__
	==~~Reference~~==		</StructureSection>
	<~~ref group="xtra">PMID:022619329<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 05:03, 29 August 2012

2012-08-29T05:03:08Z

← Older revision		Revision as of 05:03, 29 August 2012
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	[[Image:4eut.~~jpg~~\|left\|200px]]		[[Image:4eut.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4eut", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
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	{{STRUCTURE_4eut\| PDB=4eut \| SCENE= }}		{{STRUCTURE_4eut\| PDB=4eut \| SCENE= }}

	===Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain===		===Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain===

			{{ABSTRACT_PUBMED_22619329}}

	==About this Structure==		==About this Structure==
	[[4eut]] is a 2 chain structure with 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=4EUT OCA].		[[4eut]] is a 2 chain structure with 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=4EUT OCA].

			==Reference==
			<ref group="xtra">PMID:022619329</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 06:18, 23 May 2012

2012-05-23T06:18:28Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4eut.jpg|left|200px]]
-The entry 4eut is ON HOLD
+<!--
-Authors: Ma, X., Helgason, E., Phung, Q.T., Quan, C.L., Iyer, R.S., Lee, M.W., Bowman, K.K., Starovasnik, M.A., Dueber, E.C.
+===Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain===
-Description: Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain

OCA: Protected "4eut" [edit=sysop:move=sysop]

2012-05-02T19:00:18Z

Protected "4eut" [edit=sysop:move=sysop]

← Older revision	Revision as of 19:00, 2 May 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4eut is ON HOLD Authors: Ma, X., Helgason, E., Phung, Q.T., Quan, C.L., Iyer, R.S., Lee, M.W., Bowman, K.K., Starovasnik, M.A., Dueber, E.C. Descri...

2012-05-02T19:00:17Z

New page: '''Unreleased structure''' The entry 4eut is ON HOLD Authors: Ma, X., Helgason, E., Phung, Q.T., Quan, C.L., Iyer, R.S., Lee, M.W., Bowman, K.K., Starovasnik, M.A., Dueber, E.C. Descri...

New page

'''Unreleased structure'''

The entry 4eut is ON HOLD

Authors: Ma, X., Helgason, E., Phung, Q.T., Quan, C.L., Iyer, R.S., Lee, M.W., Bowman, K.K., Starovasnik, M.A., Dueber, E.C.

Description: Structure of BX-795 Complexed with Unphosphorylated Human TBK1 Kinase-ULD Domain