7q8v - Revision history

OCA at 13:15, 1 February 2024

OCA — Thu, 01 Feb 2024 13:15:29 GMT

←Older revision		Revision as of 13:15, 1 February 2024
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	==Crystal structure of TTBK1 in complex with VNG2.73 (compound 42)==		==Crystal structure of TTBK1 in complex with VNG2.73 (compound 42)==
-	<StructureSection load='7q8v' size='340' side='right'caption='[[7q8v]]' scene=''>	+	<StructureSection load='7q8v' size='340' side='right'caption='[[7q8v]], [[Resolution\|resolution]] 2.13Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q8V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7q8v]] 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=7Q8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q8V FirstGlance]. <br>
-	</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=7q8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q8v OCA], [https://pdbe.org/7q8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q8v RCSB], [https://www.ebi.ac.uk/pdbsum/7q8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q8v ProSAT]</span></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]] 2.13Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9IV:~{N}-[4-(2-chloranylphenoxy)phenyl]-7~{H}-pyrrolo[2,3-d]pyrimidin-4-amine'>9IV</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=7q8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q8v OCA], [https://pdbe.org/7q8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q8v RCSB], [https://www.ebi.ac.uk/pdbsum/7q8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q8v ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease without any effective treatment. Protein TDP-43 is a pathological hallmark of ALS in both sporadic and familiar patients. Post-translational modifications of TDP-43 promote its aggregation in the cytoplasm. Tau-Tubulin kinase (TTBK1) phosphorylates TDP-43 in cellular and animal models; thus, TTBK1 inhibitors emerge as a promising therapeutic strategy for ALS. The design, synthesis, biological evaluation, kinase-ligand complex structure determination, and molecular modeling studies confirmed novel pyrrolopyrimidine derivatives as valuable inhibitors for further development. Moreover, compound 29 revealed good brain penetration in vivo and was able to reduce TDP-43 phosphorylation not only in cell cultures but also in the spinal cord of transgenic TDP-43 mice. A shift to M2 anti-inflammatory microglia was also demonstrated in vivo. Both these activities led to motor neuron preservation in mice, proposing pyrrolopyrimidine 29 as a valuable lead compound for future ALS therapy.
		+
		+	TDP-43 Modulation by Tau-Tubulin Kinase 1 Inhibitors: A New Avenue for Future Amyotrophic Lateral Sclerosis Therapy.,Nozal V, Martinez-Gonzalez L, Gomez-Almeria M, Gonzalo-Consuegra C, Santana P, Chaikuad A, Perez-Cuevas E, Knapp S, Lietha D, Ramirez D, Petralla S, Monti B, Gil C, Martin-Requero A, Palomo V, de Lago E, Martinez A J Med Chem. 2022 Jan 27;65(2):1585-1607. doi: 10.1021/acs.jmedchem.1c01942. Epub , 2022 Jan 3. PMID:34978799<ref>PMID:34978799</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7q8v" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chaikuad A]]		[[Category: Chaikuad A]]

OCA at 06:06, 9 March 2022

OCA — Wed, 09 Mar 2022 06:06:26 GMT

←Older revision		Revision as of 06:06, 9 March 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7q8v ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of TTBK1 in complex with VNG2.73 (compound 42)==
-		+	<StructureSection load='7q8v' size='340' side='right'caption='[[7q8v]]' scene=''>
-	~~Authors~~: ~~Chaikuad~~, A., ~~Nozal, V~~., ~~Martinez, A~~., ~~Knapp, S~~., ~~Structural Genomics Consortium (SGC)~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q8V FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of TTBK1 in complex with VNG2~~.~~73 (compound 42)~~	+	</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=7q8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q8v OCA], [https://pdbe.org/7q8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q8v RCSB], [https://www.ebi.ac.uk/pdbsum/7q8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q8v ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Chaikuad, A]]	+	__TOC__
-	[[Category: Knapp, S]]	+	</StructureSection>
-	[[Category: Martinez, A]]	+	[[Category: Large Structures]]
-	~~[[Category: Structural Genomics Consortium (Sgc)~~]]	+	[[Category: Chaikuad A]]
-	[[Category: Nozal, V]]	+	[[Category: Knapp S]]
		+	[[Category: Martinez A]]
		+	[[Category: Nozal V]]

OCA at 15:31, 15 December 2021

OCA — Wed, 15 Dec 2021 15:31:46 GMT

←Older revision		Revision as of 15:31, 15 December 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7q8v is ON HOLD	+	The entry 7q8v is ON HOLD until Paper Publication

	Authors: Chaikuad, A., Nozal, V., Martinez, A., Knapp, S., Structural Genomics Consortium (SGC)		Authors: Chaikuad, A., Nozal, V., Martinez, A., Knapp, S., Structural Genomics Consortium (SGC)
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	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Chaikuad, A]]		[[Category: Chaikuad, A]]
-	[[Category: Martinez, A]]
	[[Category: Knapp, S]]		[[Category: Knapp, S]]
		+	[[Category: Martinez, A]]
	[[Category: Structural Genomics Consortium (Sgc)]]		[[Category: Structural Genomics Consortium (Sgc)]]
	[[Category: Nozal, V]]		[[Category: Nozal, V]]

OCA: Protected "7q8v" [edit=sysop:move=sysop]

OCA — Wed, 17 Nov 2021 12:08:25 GMT

Protected "7q8v" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:08, 17 November 2021

OCA: New page: '''Unreleased structure''' The entry 7q8v is ON HOLD Authors: Chaikuad, A., Nozal, V., Martinez, A., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of T...

OCA — Wed, 17 Nov 2021 12:08:23 GMT

New page: '''Unreleased structure''' The entry 7q8v is ON HOLD Authors: Chaikuad, A., Nozal, V., Martinez, A., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of T...

New page

'''Unreleased structure'''

The entry 7q8v is ON HOLD

Authors: Chaikuad, A., Nozal, V., Martinez, A., Knapp, S., Structural Genomics Consortium (SGC)

Description: Crystal structure of TTBK1 in complex with VNG2.73 (compound 42)
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Martinez, A]]
[[Category: Knapp, S]]
[[Category: Structural Genomics Consortium (Sgc)]]
[[Category: Nozal, V]]