7q90 - Revision history

OCA at 13:15, 1 February 2024

2024-02-01T13:15:34Z

←Older revision		Revision as of 13:15, 1 February 2024
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	==Crystal structure of TTBK2 in complex with VNG1.63 (compound 32)==		==Crystal structure of TTBK2 in complex with VNG1.63 (compound 32)==
-	<StructureSection load='7q90' size='340' side='right'caption='[[7q90]]' scene=''>	+	<StructureSection load='7q90' size='340' side='right'caption='[[7q90]], [[Resolution\|resolution]] 1.60Å' 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=7Q90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q90 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7q90]] 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=7Q90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q90 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=7q90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q90 OCA], [https://pdbe.org/7q90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q90 RCSB], [https://www.ebi.ac.uk/pdbsum/7q90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q90 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]] 1.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9IS:~{N}-[4-(4-methoxyphenoxy)phenyl]-7~{H}-pyrrolo[2,3-d]pyrimidin-4-amine'>9IS</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=7q90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q90 OCA], [https://pdbe.org/7q90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q90 RCSB], [https://www.ebi.ac.uk/pdbsum/7q90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q90 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/TTBK2_HUMAN TTBK2_HUMAN] Spinocerebellar ataxia type 11. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/TTBK2_HUMAN TTBK2_HUMAN] Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro.<ref>PMID:21548880</ref> <ref>PMID:23141541</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 7q90" 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

2022-03-09T06:06:32Z

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

-	~~The entry~~ 7q90 ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of TTBK2 in complex with VNG1.63 (compound 32)==
-		+	<StructureSection load='7q90' size='340' side='right'caption='[[7q90]]' 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=7Q90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q90 FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of TTBK2 in complex with VNG1~~.~~63 (compound 32)~~	+	</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=7q90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q90 OCA], [https://pdbe.org/7q90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q90 RCSB], [https://www.ebi.ac.uk/pdbsum/7q90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q90 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

2021-12-15T15:31:55Z

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

-	The entry 7q90 is ON HOLD	+	The entry 7q90 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 "7q90" [edit=sysop:move=sysop]

2021-11-17T12:08:58Z

Protected "7q90" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:08, 17 November 2021

OCA: New page: '''Unreleased structure''' The entry 7q90 is ON HOLD Authors: Chaikuad, A., Nozal, V., Martinez, A., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of T...

2021-11-17T12:08:56Z

New page: '''Unreleased structure''' The entry 7q90 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 7q90 is ON HOLD

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

Description: Crystal structure of TTBK2 in complex with VNG1.63 (compound 32)
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Martinez, A]]
[[Category: Knapp, S]]
[[Category: Structural Genomics Consortium (Sgc)]]
[[Category: Nozal, V]]