4iwo - Revision history

OCA at 12:00, 1 March 2024

OCA — Fri, 01 Mar 2024 12:00:08 GMT

←Older revision		Revision as of 12:00, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4iwo]] is a 1 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=4IWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IWO FirstGlance]. <br>		<table><tr><td colspan='2'>[[4iwo]] is a 1 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=4IWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IWO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1H4:N-{3-[(5-CYCLOPROPYL-2-{[3-(2-OXOPYRROLIDIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)AMINO]PROPYL}CYCLOBUTANECARBOXAMIDE'>1H4</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]] 2.61Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1H4:N-{3-[(5-CYCLOPROPYL-2-{[3-(2-OXOPYRROLIDIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)AMINO]PROPYL}CYCLOBUTANECARBOXAMIDE'>1H4</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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [https://pdbe.org/4iwo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [https://www.ebi.ac.uk/pdbsum/4iwo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iwo 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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [https://pdbe.org/4iwo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [https://www.ebi.ac.uk/pdbsum/4iwo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iwo 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 I (TBK1) plays a key role in the innate immune system by integrating signals from pattern-recognition receptors. Here, we report the X-ray crystal structures of inhibitor-bound inactive and active TBK1 determined to 2.6 A and 4.0 A resolution, respectively. The structures reveal a compact dimer made up of trimodular subunits containing an N-terminal kinase domain (KD), a ubiquitin-like domain (ULD), and an alpha-helical scaffold dimerization domain (SDD). Activation rearranges the KD into an active conformation while maintaining the overall dimer conformation. Low-resolution SAXS studies reveal that the missing C-terminal domain (CTD) extends away from the main body of the kinase dimer. Mutants that interfere with TBK1 dimerization show significantly reduced trans-autophosphorylation but retain the ability to bind adaptor proteins through the CTD. Our results provide detailed insights into the architecture of TBK1 and the molecular mechanism of activation.
-
-	Crystal structure and mechanism of activation of TANK-binding kinase 1.,Larabi A, Devos JM, Ng SL, Nanao MH, Round A, Maniatis T, Panne D Cell Rep. 2013 Mar 28;3(3):734-46. doi: 10.1016/j.celrep.2013.01.034. Epub 2013, Feb 28. PMID:23453971<ref>PMID:23453971</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4iwo" style="background-color:#fffaf0;"></div>

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

OCA at 21:16, 16 November 2022

OCA — Wed, 16 Nov 2022 21:16:23 GMT

←Older revision		Revision as of 21:16, 16 November 2022
Line 1:		Line 1:

	==Crystal structure and mechanism of activation of TBK1==		==Crystal structure and mechanism of activation of TBK1==
-	<StructureSection load='4iwo' size='340' side='right' caption='[[4iwo]], [[Resolution\|resolution]] 2.61Å' scene=''>	+	<StructureSection load='4iwo' size='340' side='right'caption='[[4iwo]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4iwo]] is a 1 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=4IWO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4IWO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4iwo]] is a 1 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=4IWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IWO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1H4:N-{3-[(5-CYCLOPROPYL-2-{[3-(2-OXOPYRROLIDIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)AMINO]PROPYL}CYCLOBUTANECARBOXAMIDE'>1H4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1H4:N-{3-[(5-CYCLOPROPYL-2-{[3-(2-OXOPYRROLIDIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)AMINO]PROPYL}CYCLOBUTANECARBOXAMIDE'>1H4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4iw0\|4iw0]], [[4iwp\|4iwp]], [[4iwq\|4iwq]]</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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [https://pdbe.org/4iwo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [https://www.ebi.ac.uk/pdbsum/4iwo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iwo ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NAK, TBK1 ([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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [~~http~~://pdbe.org/4iwo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4iwo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4iwo 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 ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]	+	*[[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: Larabi, A]]	+	[[Category: Larabi A]]
-	[[Category: Panne, D]]	+	[[Category: Panne D]]
-	~~[[Category: Atp binding]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 19:13, 5 August 2016

OCA — Fri, 05 Aug 2016 19:13:06 GMT

←Older revision		Revision as of 19:13, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure and mechanism of activation of TBK1==		==Crystal structure and mechanism of activation of TBK1==
	<StructureSection load='4iwo' size='340' side='right' caption='[[4iwo]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='4iwo' size='340' side='right' caption='[[4iwo]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4iwo]] is a 1 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=4IWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IWO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4iwo]] is a 1 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=4IWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IWO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1H4:N-{3-[(5-CYCLOPROPYL-2-{[3-(2-OXOPYRROLIDIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)AMINO]PROPYL}CYCLOBUTANECARBOXAMIDE'>1H4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1H4:N-{3-[(5-CYCLOPROPYL-2-{[3-(2-OXOPYRROLIDIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)AMINO]PROPYL}CYCLOBUTANECARBOXAMIDE'>1H4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4iw0\|4iw0]], [[4iwp\|4iwp]], [[4iwq\|4iwq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4iw0\|4iw0]], [[4iwp\|4iwp]], [[4iwq\|4iwq]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NAK, TBK1 ([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">NAK, TBK1 ([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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [http://www.ebi.ac.uk/pdbsum/4iwo 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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [http://pdbe.org/4iwo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [http://www.ebi.ac.uk/pdbsum/4iwo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iwo ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 4iwo" 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: Larabi, A]]		[[Category: Larabi, A]]

OCA at 05:07, 25 December 2014

OCA — Thu, 25 Dec 2014 05:07:17 GMT

←Older revision		Revision as of 05:07, 25 December 2014
Line 9:		Line 9:
	<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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [http://www.ebi.ac.uk/pdbsum/4iwo 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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [http://www.ebi.ac.uk/pdbsum/4iwo 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 ==

OCA at 13:00, 21 December 2014

OCA — Sun, 21 Dec 2014 13:00:58 GMT

←Older revision		Revision as of 13:00, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4iwo\| PDB=4iwo \| SCENE= }}~~	+	==Crystal structure and mechanism of activation of TBK1==
-	===Crystal structure and mechanism of activation of TBK1===	+	<StructureSection load='4iwo' size='340' side='right' caption='[[4iwo]], [[Resolution\|resolution]] 2.61Å' scene=''>
-	{{~~ABSTRACT_PUBMED_23453971~~}}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4iwo]] is a 1 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=4IWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IWO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1H4:N-{3-[(5-CYCLOPROPYL-2-{[3-(2-OXOPYRROLIDIN-1-YL)PHENYL]AMINO}PYRIMIDIN-4-YL)AMINO]PROPYL}CYCLOBUTANECARBOXAMIDE'>1H4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4iw0\|4iw0]], [[4iwp\|4iwp]], [[4iwq\|4iwq]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NAK, TBK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iwo RCSB], [http://www.ebi.ac.uk/pdbsum/4iwo PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tank-binding kinase I (TBK1) plays a key role in the innate immune system by integrating signals from pattern-recognition receptors. Here, we report the X-ray crystal structures of inhibitor-bound inactive and active TBK1 determined to 2.6 A and 4.0 A resolution, respectively. The structures reveal a compact dimer made up of trimodular subunits containing an N-terminal kinase domain (KD), a ubiquitin-like domain (ULD), and an alpha-helical scaffold dimerization domain (SDD). Activation rearranges the KD into an active conformation while maintaining the overall dimer conformation. Low-resolution SAXS studies reveal that the missing C-terminal domain (CTD) extends away from the main body of the kinase dimer. Mutants that interfere with TBK1 dimerization show significantly reduced trans-autophosphorylation but retain the ability to bind adaptor proteins through the CTD. Our results provide detailed insights into the architecture of TBK1 and the molecular mechanism of activation.

-	~~==Function==~~	+	Crystal structure and mechanism of activation of TANK-binding kinase 1.,Larabi A, Devos JM, Ng SL, Nanao MH, Round A, Maniatis T, Panne D Cell Rep. 2013 Mar 28;3(3):734-46. doi: 10.1016/j.celrep.2013.01.034. Epub 2013, Feb 28. PMID:23453971<ref>PMID:23453971</ref>
-	[[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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4iwo]] is~~ a ~~1 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=4IWO OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023453971</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Larabi, A.]]	+	[[Category: Larabi, A]]
-	[[Category: Panne, D.]]	+	[[Category: Panne, D]]
	[[Category: Atp binding]]		[[Category: Atp binding]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 17:57, 19 June 2013

OCA — Wed, 19 Jun 2013 17:57:11 GMT

←Older revision		Revision as of 17:57, 19 June 2013
Line 1:		Line 1:
	{{STRUCTURE_4iwo\| PDB=4iwo \| SCENE= }}		{{STRUCTURE_4iwo\| PDB=4iwo \| SCENE= }}
	===Crystal structure and mechanism of activation of TBK1===		===Crystal structure and mechanism of activation of TBK1===
		+	{{ABSTRACT_PUBMED_23453971}}

	==Function==		==Function==
Line 9:		Line 10:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:023453971</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 09:37, 24 April 2013

OCA — Wed, 24 Apr 2013 09:37:11 GMT

←Older revision		Revision as of 09:37, 24 April 2013
Line 1:		Line 1:
	{{STRUCTURE_4iwo\| PDB=4iwo \| SCENE= }}		{{STRUCTURE_4iwo\| PDB=4iwo \| SCENE= }}
	===Crystal structure and mechanism of activation of TBK1===		===Crystal structure and mechanism of activation of TBK1===
		+
		+	==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>

	==About this Structure==		==About this Structure==
	[[4iwo]] is a 1 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=4IWO OCA].		[[4iwo]] is a 1 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=4IWO OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 10:32, 13 March 2013

OCA — Wed, 13 Mar 2013 10:32:09 GMT

←Older revision		Revision as of 10:32, 13 March 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4iwo\| PDB=4iwo \| SCENE= }}
		+	===Crystal structure and mechanism of activation of TBK1===

-	~~The entry~~ 4iwo is ~~ON HOLD until Paper Publication~~	+	==About this Structure==
-		+	[[4iwo]] is a 1 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=4IWO OCA].
-	~~Authors~~: ~~Panne, D.,~~ Larabi, A.	+	[[Category: Homo sapiens]]
-		+	[[Category: Non-specific serine/threonine protein kinase]]
-	~~Description~~: ~~Crystal structure and mechanism of activation of TBK1~~	+	[[Category: Larabi, A.]]
		+	[[Category: Panne, D.]]
		+	[[Category: Atp binding]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 13:27, 20 February 2013

OCA — Wed, 20 Feb 2013 13:27:07 GMT

←Older revision		Revision as of 13:27, 20 February 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4iwo is ON HOLD	+	The entry 4iwo is ON HOLD until Paper Publication

	Authors: Panne, D., Larabi, A.		Authors: Panne, D., Larabi, A.

	Description: Crystal structure and mechanism of activation of TBK1		Description: Crystal structure and mechanism of activation of TBK1

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

OCA — Wed, 30 Jan 2013 12:07:26 GMT

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

←Older revision

Revision as of 12:07, 30 January 2013