6q2a - Revision history

OCA at 07:39, 11 October 2023

OCA — Wed, 11 Oct 2023 07:39:46 GMT

←Older revision		Revision as of 07:39, 11 October 2023
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	<StructureSection load='6q2a' size='340' side='right'caption='[[6q2a]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='6q2a' size='340' side='right'caption='[[6q2a]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6q2a]] is a 16 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Tryb2 Tryb2~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q2A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6Q2A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6q2a]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q2A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5XH:~{N}-[1-[(3~{R})-1-[4-(DIMETHYLAMINO)BUT-2-ENOYL]AZEPAN-3-YL]-7-METHYL-BENZIMIDAZOL-2-YL]-2-METHYL-PYRIDINE-4-CARBOXAMIDE'>5XH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.6Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tb11.01.4230 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=185431 TRYB2])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5XH:~{N}-[1-[(3~{R})-1-[4-(DIMETHYLAMINO)BUT-2-ENOYL]AZEPAN-3-YL]-7-METHYL-BENZIMIDAZOL-2-YL]-2-METHYL-PYRIDINE-4-CARBOXAMIDE'>5XH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6q2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q2a OCA], [~~http~~://pdbe.org/6q2a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6q2a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6q2a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6q2a 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=6q2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q2a OCA], [https://pdbe.org/6q2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q2a RCSB], [https://www.ebi.ac.uk/pdbsum/6q2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q2a ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q382U0_TRYB2 Q382U0_TRYB2]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Tryb2~~]]	+	[[Category: Trypanosoma brucei brucei TREU927]]
-	[[Category: Ma, X]]	+	[[Category: Ma X]]
-	[[Category: Ornelas, E]]	+	[[Category: Ornelas E]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 11:32, 29 July 2020

OCA — Wed, 29 Jul 2020 11:32:40 GMT

←Older revision		Revision as of 11:32, 29 July 2020
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	==Trypanosoma brucei CLK1 kinase domain in complex with a covalent aminobenzimidazole inhibitor AB1==		==Trypanosoma brucei CLK1 kinase domain in complex with a covalent aminobenzimidazole inhibitor AB1==
-	<StructureSection load='6q2a' size='340' side='right'caption='[[6q2a]]' scene=''>	+	<StructureSection load='6q2a' size='340' side='right'caption='[[6q2a]], [[Resolution\|resolution]] 2.60Å' 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=6Q2A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Q2A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6q2a]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Tryb2 Tryb2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q2A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Q2A FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6q2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q2a OCA], [http://pdbe.org/6q2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q2a RCSB], [http://www.ebi.ac.uk/pdbsum/6q2a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q2a ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5XH:~{N}-[1-[(3~{R})-1-[4-(DIMETHYLAMINO)BUT-2-ENOYL]AZEPAN-3-YL]-7-METHYL-BENZIMIDAZOL-2-YL]-2-METHYL-PYRIDINE-4-CARBOXAMIDE'>5XH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tb11.01.4230 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=185431 TRYB2])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6q2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q2a OCA], [http://pdbe.org/6q2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q2a RCSB], [http://www.ebi.ac.uk/pdbsum/6q2a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q2a ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The kinetochore is a macromolecular structure that assembles on the centromeres of chromosomes and provides the major attachment point for spindle microtubules during mitosis. In Trypanosoma brucei, the proteins that make up the kinetochore are highly divergent; the inner kinetochore comprises at least 20 distinct and essential proteins (KKT1-20) that include four protein kinases-CLK1 (also known as KKT10), CLK2 (also known as KKT19), KKT2 and KKT3. Here, we report the identification and characterization of the amidobenzimidazoles (AB) protein kinase inhibitors that show nanomolar potency against T. brucei bloodstream forms, Leishmania and Trypanosoma cruzi. We performed target deconvolution analysis using a selection of 29 T. brucei mutants that overexpress known essential protein kinases, and identified CLK1 as a primary target. Biochemical studies and the co-crystal structure of CLK1 in complex with AB1 show that the irreversible competitive inhibition of CLK1 is dependent on a Michael acceptor forming an irreversible bond with Cys 215 in the ATP-binding pocket, a residue that is not present in human CLK1, thereby providing selectivity. Chemical inhibition of CLK1 impairs inner kinetochore recruitment and compromises cell-cycle progression, leading to cell death. This research highlights a unique drug target for trypanosomatid parasitic protozoa and a new chemical tool for investigating the function of their divergent kinetochores.
		+
		+	Targeting the trypanosome kinetochore with CLK1 protein kinase inhibitors.,Saldivia M, Fang E, Ma X, Myburgh E, Carnielli JBT, Bower-Lepts C, Brown E, Ritchie R, Lakshminarayana SB, Chen YL, Patra D, Ornelas E, Koh HXY, Williams SL, Supek F, Paape D, McCulloch R, Kaiser M, Barrett MP, Jiricek J, Diagana TT, Mottram JC, Rao SPS Nat Microbiol. 2020 Jul 13. pii: 10.1038/s41564-020-0745-6. doi:, 10.1038/s41564-020-0745-6. PMID:32661312<ref>PMID:32661312</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6q2a" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ma X]]	+	[[Category: Tryb2]]
-	[[Category: Ornelas E]]	+	[[Category: Ma, X]]
		+	[[Category: Ornelas, E]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 10:10, 17 June 2020

OCA — Wed, 17 Jun 2020 10:10:19 GMT

←Older revision		Revision as of 10:10, 17 June 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6q2a ~~is ON HOLD until Paper Publication~~	+	==Trypanosoma brucei CLK1 kinase domain in complex with a covalent aminobenzimidazole inhibitor AB1==
-		+	<StructureSection load='6q2a' size='340' side='right'caption='[[6q2a]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q2A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Q2A FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6q2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q2a OCA], [http://pdbe.org/6q2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q2a RCSB], [http://www.ebi.ac.uk/pdbsum/6q2a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q2a ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Ma X]]
		+	[[Category: Ornelas E]]

OCA at 07:18, 2 October 2019

OCA — Wed, 02 Oct 2019 07:18:46 GMT

←Older revision		Revision as of 07:18, 2 October 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6q2a is ON HOLD	+	The entry 6q2a is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6q2a" [edit=sysop:move=sysop]

OCA — Wed, 14 Aug 2019 15:06:59 GMT

Protected "6q2a" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:06, 14 August 2019

OCA: New page: '''Unreleased structure''' The entry 6q2a is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 14 Aug 2019 15:06:58 GMT

New page: '''Unreleased structure''' The entry 6q2a is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6q2a is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]