4btj - Revision history

OCA at 11:05, 9 May 2024

OCA — Thu, 09 May 2024 11:05:08 GMT

←Older revision		Revision as of 11:05, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4btj]] 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=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4btj]] 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=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.16Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [https://pdbe.org/4btj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [https://www.ebi.ac.uk/pdbsum/4btj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btj 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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [https://pdbe.org/4btj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [https://www.ebi.ac.uk/pdbsum/4btj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/TTBK1_HUMAN TTBK1_HUMAN]] Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.<ref>PMID:16923168</ref>	+	[https://www.uniprot.org/uniprot/TTBK1_HUMAN TTBK1_HUMAN] Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.<ref>PMID:16923168</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tau-tubulin kinase 1 (TTBK1) is a serine/threonine/tyrosine kinase that putatively phosphorylates residues including S422 in tau protein. Hyperphosphorylation of tau protein is the primary cause of tau pathology and neuronal death associated with Alzheimer's disease. A library of 12 truncation variants comprising the TTBK1 kinase domain was screened for expression in Escherichia coli and insect cells. One variant (residues 14-313) could be purified, but mass spectrometric analysis revealed extensive phosphorylation of the protein. Co-expression with lambda phosphatase in E. coli resulted in production of homogeneous, nonphosphorylated TTBK1. Binding of ATP and several compounds to TTBK1 was characterized by surface plasmon resonance. Crystal structures of TTBK1 in the unliganded form and in complex with ATP, and two high-affinity ATP-competitive inhibitors, 3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol (1) and methyl 2-bromo-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzoate (2), were elucidated. The structure revealed two clear basic patches near the ATP pocket providing an explanation of TTBK1 for phosphorylation-primed substrates. Interestingly, compound 2 displayed slow binding kinetics to TTBK1, the structure of TTBK1 in complex with this compound revealed a reorganization of the L199-D200 peptide backbone conformation together with altered hydrogen bonding with compound 2. These conformational changes necessary for the binding of compound 2 are likely the basis of the slow kinetics. This first TTBK1 structure can assist the discovery of novel inhibitors for the treatment of Alzheimer's disease.
		+
		+	X-ray Structural Analysis of Tau-Tubulin Kinase 1 and Its Interactions with Small Molecular Inhibitors.,Xue Y, Wan PT, Hillertz P, Schweikart F, Zhao Y, Wissler L, Dekker N ChemMedChem. 2013 Sep 13. doi: 10.1002/cmdc.201300274. PMID:24039150<ref>PMID:24039150</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4btj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tau-tubulin kinase 3D structures\|Tau-tubulin kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:06, 7 September 2022

OCA — Wed, 07 Sep 2022 17:06:48 GMT

←Older revision		Revision as of 17:06, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4btj' size='340' side='right'caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='4btj' size='340' side='right'caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4btj]] 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=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4btj]] 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=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btk\|4btk]], [[4btm\|4btm]]~~</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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [https://pdbe.org/4btj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [https://www.ebi.ac.uk/pdbsum/4btj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btj ProSAT]</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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [~~http~~://pdbe.org/4btj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4btj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4btj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/TTBK1_HUMAN TTBK1_HUMAN]] Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.<ref>PMID:16923168</ref>	+	[[https://www.uniprot.org/uniprot/TTBK1_HUMAN TTBK1_HUMAN]] Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.<ref>PMID:16923168</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Tau-tubulin kinase 1 (TTBK1) is a serine/threonine/tyrosine kinase that putatively phosphorylates residues including S422 in tau protein. Hyperphosphorylation of tau protein is the primary cause of tau pathology and neuronal death associated with Alzheimer's disease. A library of 12 truncation variants comprising the TTBK1 kinase domain was screened for expression in Escherichia coli and insect cells. One variant (residues 14-313) could be purified, but mass spectrometric analysis revealed extensive phosphorylation of the protein. Co-expression with lambda phosphatase in E. coli resulted in production of homogeneous, nonphosphorylated TTBK1. Binding of ATP and several compounds to TTBK1 was characterized by surface plasmon resonance. Crystal structures of TTBK1 in the unliganded form and in complex with ATP, and two high-affinity ATP-competitive inhibitors, 3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol (1) and methyl 2-bromo-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzoate (2), were elucidated. The structure revealed two clear basic patches near the ATP pocket providing an explanation of TTBK1 for phosphorylation-primed substrates. Interestingly, compound 2 displayed slow binding kinetics to TTBK1, the structure of TTBK1 in complex with this compound revealed a reorganization of the L199-D200 peptide backbone conformation together with altered hydrogen bonding with compound 2. These conformational changes necessary for the binding of compound 2 are likely the basis of the slow kinetics. This first TTBK1 structure can assist the discovery of novel inhibitors for the treatment of Alzheimer's disease.	+
-		+
-	X-ray Structural Analysis of Tau-Tubulin Kinase 1 and Its Interactions with Small Molecular Inhibitors.,Xue Y, Wan PT, Hillertz P, Schweikart F, Zhao Y, Wissler L, Dekker N ChemMedChem. 2013 Sep 13. doi: 10.1002/cmdc.201300274. PMID:24039150<ref>PMID:24039150</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4btj" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dekker, N]]	+	[[Category: Dekker N]]
-	[[Category: Hillertz, P]]	+	[[Category: Hillertz P]]
-	[[Category: Schweikart, F]]	+	[[Category: Schweikart F]]
-	[[Category: Wan, P]]	+	[[Category: Wan P]]
-	[[Category: Wissler, L]]	+	[[Category: Wissler L]]
-	[[Category: Xue, Y]]	+	[[Category: Xue Y]]
-	[[Category: Zhao, Y]]	+	[[Category: Zhao Y]]
-	~~[[Category: Ligand complex]]~~	+
-	~~[[Category: Structure-kinetics relationship]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 13:15, 13 March 2019

OCA — Wed, 13 Mar 2019 13:15:21 GMT

←Older revision		Revision as of 13:15, 13 March 2019
Line 1:		Line 1:

	==TTBK1 in complex with ATP==		==TTBK1 in complex with ATP==
-	<StructureSection load='4btj' size='340' side='right' caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>	+	<StructureSection load='4btj' size='340' side='right'caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4btj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4btj]] 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=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btk\|4btk]], [[4btm\|4btm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btk\|4btk]], [[4btm\|4btm]]</td></tr>
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Dekker, N]]		[[Category: Dekker, N]]
	[[Category: Hillertz, P]]		[[Category: Hillertz, P]]

OCA at 07:07, 29 March 2017

OCA — Wed, 29 Mar 2017 07:07:41 GMT

←Older revision		Revision as of 07:07, 29 March 2017
Line 3:		Line 3:
	<StructureSection load='4btj' size='340' side='right' caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='4btj' size='340' side='right' caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4btj]] 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=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4btj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btk\|4btk]], [[4btm\|4btm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btk\|4btk]], [[4btm\|4btm]]</td></tr>
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Dekker, N]]		[[Category: Dekker, N]]
	[[Category: Hillertz, P]]		[[Category: Hillertz, P]]

OCA at 08:19, 5 August 2016

OCA — Fri, 05 Aug 2016 08:19:35 GMT

←Older revision		Revision as of 08:19, 5 August 2016
Line 1:		Line 1:
		+
	==TTBK1 in complex with ATP==		==TTBK1 in complex with ATP==
	<StructureSection load='4btj' size='340' side='right' caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='4btj' size='340' side='right' caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btk\|4btk]], [[4btm\|4btm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btk\|4btk]], [[4btm\|4btm]]</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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [http://www.ebi.ac.uk/pdbsum/4btj 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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [http://pdbe.org/4btj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [http://www.ebi.ac.uk/pdbsum/4btj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4btj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4btj" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:12, 25 December 2014

OCA — Thu, 25 Dec 2014 17:12:56 GMT

←Older revision		Revision as of 17:12, 25 December 2014
Line 7:		Line 7:
	<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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [http://www.ebi.ac.uk/pdbsum/4btj 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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [http://www.ebi.ac.uk/pdbsum/4btj PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TTBK1_HUMAN TTBK1_HUMAN]] Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.<ref>PMID:16923168</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 16:42, 21 December 2014

OCA — Sun, 21 Dec 2014 16:42:58 GMT

←Older revision		Revision as of 16:42, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4btj\| PDB~~=4btj \| ~~SCENE~~= }}	+	==TTBK1 in complex with ATP==
-	===~~TTBK1 in complex~~ with ATP===	+	<StructureSection load='4btj' size='340' side='right' caption='[[4btj]], [[Resolution\|resolution]] 2.16Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24039150}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4btj]] 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=4BTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btk\|4btk]], [[4btm\|4btm]]</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=4btj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btj RCSB], [http://www.ebi.ac.uk/pdbsum/4btj PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tau-tubulin kinase 1 (TTBK1) is a serine/threonine/tyrosine kinase that putatively phosphorylates residues including S422 in tau protein. Hyperphosphorylation of tau protein is the primary cause of tau pathology and neuronal death associated with Alzheimer's disease. A library of 12 truncation variants comprising the TTBK1 kinase domain was screened for expression in Escherichia coli and insect cells. One variant (residues 14-313) could be purified, but mass spectrometric analysis revealed extensive phosphorylation of the protein. Co-expression with lambda phosphatase in E. coli resulted in production of homogeneous, nonphosphorylated TTBK1. Binding of ATP and several compounds to TTBK1 was characterized by surface plasmon resonance. Crystal structures of TTBK1 in the unliganded form and in complex with ATP, and two high-affinity ATP-competitive inhibitors, 3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol (1) and methyl 2-bromo-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzoate (2), were elucidated. The structure revealed two clear basic patches near the ATP pocket providing an explanation of TTBK1 for phosphorylation-primed substrates. Interestingly, compound 2 displayed slow binding kinetics to TTBK1, the structure of TTBK1 in complex with this compound revealed a reorganization of the L199-D200 peptide backbone conformation together with altered hydrogen bonding with compound 2. These conformational changes necessary for the binding of compound 2 are likely the basis of the slow kinetics. This first TTBK1 structure can assist the discovery of novel inhibitors for the treatment of Alzheimer's disease.

-	~~==Function==~~	+	X-ray Structural Analysis of Tau-Tubulin Kinase 1 and Its Interactions with Small Molecular Inhibitors.,Xue Y, Wan PT, Hillertz P, Schweikart F, Zhao Y, Wissler L, Dekker N ChemMedChem. 2013 Sep 13. doi: 10.1002/cmdc.201300274. PMID:24039150<ref>PMID:24039150</ref>
-	~~[[http://www~~.~~uniprot~~.~~org/uniprot~~/~~TTBK1_HUMAN TTBK1_HUMAN]] Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues~~. ~~Induces aggregation of TAU~~.<ref>PMID:~~16923168~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4btj]] 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=4BTJ OCA].~~	+	</div>
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:024039150</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Dekker, N.]]	+	[[Category: Dekker, N]]
-	[[Category: Hillertz, P.]]	+	[[Category: Hillertz, P]]
-	[[Category: Schweikart, F.]]	+	[[Category: Schweikart, F]]
-	[[Category: Wan, P.]]	+	[[Category: Wan, P]]
-	[[Category: Wissler, L.]]	+	[[Category: Wissler, L]]
-	[[Category: Xue, Y.]]	+	[[Category: Xue, Y]]
-	[[Category: Zhao, Y.]]	+	[[Category: Zhao, Y]]
	[[Category: Ligand complex]]		[[Category: Ligand complex]]
	[[Category: Structure-kinetics relationship]]		[[Category: Structure-kinetics relationship]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 08:36, 25 December 2013

OCA — Wed, 25 Dec 2013 08:36:44 GMT

←Older revision		Revision as of 08:36, 25 December 2013
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
-	[[4btj]] 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=4BTJ OCA].	+	[[4btj]] 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=4BTJ OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:024039150</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:024039150</ref><references group="xtra"/><references/>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Dekker, N.]]		[[Category: Dekker, N.]]
	[[Category: Hillertz, P.]]		[[Category: Hillertz, P.]]

OCA at 08:10, 29 September 2013

OCA — Sun, 29 Sep 2013 08:10:29 GMT

←Older revision		Revision as of 08:10, 29 September 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4btj\| PDB=4btj \| SCENE= }}
		+	===TTBK1 in complex with ATP===
		+	{{ABSTRACT_PUBMED_24039150}}

-	~~The entry 4btj~~ is ~~ON HOLD~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/TTBK1_HUMAN TTBK1_HUMAN]] Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.<ref>PMID:16923168</ref>

-	~~Authors~~: ~~Xue, Y~~.~~, Wan, P~~.~~, Hillertz, P~~.~~, Schweikart, F~~.~~, Zhao, Y~~.~~, Wissler, L~~.~~, Dekker, N~~.	+	==About this Structure==
		+	[[4btj]] 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=4BTJ OCA].

-	~~Description~~: ~~TTBK1 in~~ complex ~~with ATP~~	+	==Reference==
		+	<ref group="xtra">PMID:024039150</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Dekker, N.]]
		+	[[Category: Hillertz, P.]]
		+	[[Category: Schweikart, F.]]
		+	[[Category: Wan, P.]]
		+	[[Category: Wissler, L.]]
		+	[[Category: Xue, Y.]]
		+	[[Category: Zhao, Y.]]
		+	[[Category: Ligand complex]]
		+	[[Category: Structure-kinetics relationship]]
		+	[[Category: Transferase]]

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

OCA — Sun, 30 Jun 2013 08:29:23 GMT

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

←Older revision

Revision as of 08:29, 30 June 2013