4btk - Revision history

OCA at 11:05, 9 May 2024

OCA — Thu, 09 May 2024 11:05:07 GMT

←Older revision		Revision as of 11:05, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4btk]] 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=4BTK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTK FirstGlance]. <br>		<table><tr><td colspan='2'>[[4btk]] 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=4BTK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [https://pdbe.org/4btk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [https://www.ebi.ac.uk/pdbsum/4btk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btk 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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [https://pdbe.org/4btk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [https://www.ebi.ac.uk/pdbsum/4btk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btk 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 4btk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tau-tubulin kinase 3D structures\|Tau-tubulin kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:07, 7 September 2022

OCA — Wed, 07 Sep 2022 17:07:02 GMT

←Older revision		Revision as of 17:07, 7 September 2022
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	<StructureSection load='4btk' size='340' side='right'caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4btk' size='340' side='right'caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4btk]] 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=4BTK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BTK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4btk]] 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=4BTK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btj\|4btj]], [[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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [https://pdbe.org/4btk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [https://www.ebi.ac.uk/pdbsum/4btk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btk 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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [~~http~~://pdbe.org/4btk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4btk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4btk 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 4btk" 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: Structure-kinetics relationship]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 13:44, 13 March 2019

OCA — Wed, 13 Mar 2019 13:44:42 GMT

←Older revision		Revision as of 13:44, 13 March 2019
Line 1:		Line 1:

	==TTBK1 in complex with inhibitor==		==TTBK1 in complex with inhibitor==
-	<StructureSection load='4btk' size='340' side='right' caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='4btk' size='340' side='right'caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4btk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4btk]] 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=4BTK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btj\|4btj]], [[4btm\|4btm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btj\|4btj]], [[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 07:03, 29 March 2017

OCA — Wed, 29 Mar 2017 07:03:40 GMT

←Older revision		Revision as of 07:03, 29 March 2017
Line 3:		Line 3:
	<StructureSection load='4btk' size='340' side='right' caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4btk' size='340' side='right' caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4btk]] 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=4BTK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4btk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btj\|4btj]], [[4btm\|4btm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btj\|4btj]], [[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 21:54, 5 August 2016

OCA — Fri, 05 Aug 2016 21:54:28 GMT

←Older revision		Revision as of 21:54, 5 August 2016
Line 1:		Line 1:
		+
	==TTBK1 in complex with inhibitor==		==TTBK1 in complex with inhibitor==
	<StructureSection load='4btk' size='340' side='right' caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4btk' size='340' side='right' caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btj\|4btj]], [[4btm\|4btm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btj\|4btj]], [[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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [http://www.ebi.ac.uk/pdbsum/4btk 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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [http://pdbe.org/4btk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [http://www.ebi.ac.uk/pdbsum/4btk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4btk 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 4btk" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 22:14, 25 December 2014

OCA — Thu, 25 Dec 2014 22:14:12 GMT

←Older revision		Revision as of 22:14, 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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [http://www.ebi.ac.uk/pdbsum/4btk 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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [http://www.ebi.ac.uk/pdbsum/4btk 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 17:20, 21 December 2014

OCA — Sun, 21 Dec 2014 17:20:22 GMT

←Older revision		Revision as of 17:20, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4btk\| PDB~~=4btk \| ~~SCENE~~= }}	+	==TTBK1 in complex with inhibitor==
-	===~~TTBK1 in complex~~ with ~~inhibitor~~===	+	<StructureSection load='4btk' size='340' side='right' caption='[[4btk]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24039150}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4btk]] 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=4BTK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTK FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTQ:4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE'>DTQ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btj\|4btj]], [[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=4btk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btk RCSB], [http://www.ebi.ac.uk/pdbsum/4btk 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>
-	~~[[4btk]] 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=4BTK 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: Structure-kinetics relationship]]		[[Category: Structure-kinetics relationship]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 08:58, 25 December 2013

OCA — Wed, 25 Dec 2013 08:58:58 GMT

←Older revision		Revision as of 08:58, 25 December 2013
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
-	[[4btk]] 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=4BTK OCA].	+	[[4btk]] 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=4BTK 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 08:13, 29 September 2013

OCA — Sun, 29 Sep 2013 08:13:39 GMT

←Older revision		Revision as of 08:13, 29 September 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4btk\| PDB=4btk \| SCENE= }}
		+	===TTBK1 in complex with inhibitor===
		+	{{ABSTRACT_PUBMED_24039150}}

-	~~The entry 4btk~~ 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==
		+	[[4btk]] 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=4BTK OCA].

-	~~Description~~: ~~TTBK1 in complex with inhibitor~~	+	==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: Structure-kinetics relationship]]
		+	[[Category: Transferase]]

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

OCA — Sun, 30 Jun 2013 08:29:25 GMT

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

←Older revision

Revision as of 08:29, 30 June 2013