7avq - Revision history

OCA at 12:17, 1 February 2024

2024-02-01T12:17:11Z

←Older revision		Revision as of 12:17, 1 February 2024
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	<StructureSection load='7avq' size='340' side='right'caption='[[7avq]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='7avq' size='340' side='right'caption='[[7avq]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7avq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AVQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7avq]] 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=7AVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AVQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=S1Z:(2~{R})-2-[[3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-6-yl]amino]butan-1-ol'>S1Z</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]] 1.65Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HASPIN, GSG2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=S1Z:(2~{R})-2-[[3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-6-yl]amino]butan-1-ol'>S1Z</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=7avq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7avq OCA], [https://pdbe.org/7avq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7avq RCSB], [https://www.ebi.ac.uk/pdbsum/7avq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7avq 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=7avq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7avq OCA], [https://pdbe.org/7avq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7avq RCSB], [https://www.ebi.ac.uk/pdbsum/7avq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7avq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/HASP_HUMAN HASP_HUMAN]] Serine/threonine-protein kinase that phosphorylates histone H3 at 'Ser-3' (H3T3ph) during mitosis. This positions and activates AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.<ref>PMID:11228240</ref> <ref>PMID:15681610</ref> <ref>PMID:17084365</ref> <ref>PMID:20705812</ref> <ref>PMID:20929775</ref>	+	[https://www.uniprot.org/uniprot/HASP_HUMAN HASP_HUMAN] Serine/threonine-protein kinase that phosphorylates histone H3 at 'Ser-3' (H3T3ph) during mitosis. This positions and activates AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.<ref>PMID:11228240</ref> <ref>PMID:15681610</ref> <ref>PMID:17084365</ref> <ref>PMID:20705812</ref> <ref>PMID:20929775</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 7avq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7avq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Bonnet P]]
-	[[Category: Bonnet, P]]	+	[[Category: Chaikuad A]]
-	[[Category: Chaikuad, A]]	+	[[Category: Knapp S]]
-	[[Category: Knapp, S]]	+	[[Category: Routier S]]
-	[[Category: Routier, S]]	+
-	~~[[Category: Structural genomic]]~~	+
-	~~[[Category: Gsg2]]~~	+
-	~~[[Category: Haspin]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 10:03, 8 December 2021

2021-12-08T10:03:22Z

←Older revision		Revision as of 10:03, 8 December 2021
Line 1:		Line 1:

	==Crystal structure of haspin in complex with disubstituted imidazo[1,2- b]pyridazine inhibitor (compound 12)==		==Crystal structure of haspin in complex with disubstituted imidazo[1,2- b]pyridazine inhibitor (compound 12)==
-	<StructureSection load='7avq' size='340' side='right'caption='[[7avq]]' scene=''>	+	<StructureSection load='7avq' size='340' side='right'caption='[[7avq]], [[Resolution\|resolution]] 1.65Å' 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=7AVQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7AVQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7avq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AVQ 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=7avq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7avq OCA], [~~http~~://pdbe.org/7avq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7avq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7avq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7avq 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=S1Z:(2~{R})-2-[[3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-6-yl]amino]butan-1-ol'>S1Z</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HASPIN, GSG2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=7avq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7avq OCA], [https://pdbe.org/7avq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7avq RCSB], [https://www.ebi.ac.uk/pdbsum/7avq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7avq ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/HASP_HUMAN HASP_HUMAN]] Serine/threonine-protein kinase that phosphorylates histone H3 at 'Ser-3' (H3T3ph) during mitosis. This positions and activates AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.<ref>PMID:11228240</ref> <ref>PMID:15681610</ref> <ref>PMID:17084365</ref> <ref>PMID:20705812</ref> <ref>PMID:20929775</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Haspin is a mitotic protein kinase required for proper cell division by modulating Aurora B kinase localisation and activity as well as histone phosphorylation. Here a series of imidazopyridazines based on the CHR-6494 and Structure Activity Relationship was established. An assessment of the inhibitory activity of the lead structures on human Haspin and several other protein kinases is presented. The lead structure was rapidly optimised using a combination of crystal structures and effective docking models, with the best inhibitors exhibiting potent inhibitory activity on Haspin with IC50 between 6 and 100 nM in vitro. The developed inhibitors displayed anti-proliferative properties against various human cancer cell lines in 2D and spheroid cultures and significantly inhibited the migration ability of osteosarcoma U-2 OS cells. Notably, we show that our lead compounds are powerful Haspin inhibitors in human cells, and did not block G2/M cell cycle transition due to improved selectivity against CDK1/CyclinB.
		+
		+	Design of new disubstituted imidazo[1,2-b]pyridazine derivatives as selective Haspin inhibitors. Synthesis, binding mode and anticancer biological evaluation.,Elie J, Feizbakhsh O, Desban N, Josselin B, Baratte B, Bescond A, Duez J, Fant X, Bach S, Marie D, Place M, Ben Salah S, Chartier A, Berteina-Raboin S, Chaikuad A, Knapp S, Carles F, Bonnet P, Buron F, Routier S, Ruchaud S J Enzyme Inhib Med Chem. 2020 Dec;35(1):1840-1853. doi:, 10.1080/14756366.2020.1825408. PMID:33040634<ref>PMID:33040634</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7avq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chaikuad A]]	+	[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Knapp S]]	+	[[Category: Bonnet, P]]
-	[[Category: Routier S]]	+	[[Category: Chaikuad, A]]
		+	[[Category: Knapp, S]]
		+	[[Category: Routier, S]]
		+	[[Category: Structural genomic]]
		+	[[Category: Gsg2]]
		+	[[Category: Haspin]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Sgc]]
		+	[[Category: Transferase]]

OCA at 09:40, 18 November 2020

2020-11-18T09:40:31Z

←Older revision		Revision as of 09:40, 18 November 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7avq is ON HOLD~~	+	==Crystal structure of haspin in complex with disubstituted imidazo[1,2- b]pyridazine inhibitor (compound 12)==
-		+	<StructureSection load='7avq' size='340' side='right'caption='[[7avq]]' scene=''>
-	~~Authors: Chaikuad, A., Routier, S., 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=7AVQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AVQ FirstGlance]. <br>
-	~~Description:~~ Crystal structure of haspin in complex with disubstituted imidazo[1,2-b]pyridazine inhibitor (compound 12)	+	</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=7avq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7avq OCA], [http://pdbe.org/7avq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7avq RCSB], [http://www.ebi.ac.uk/pdbsum/7avq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7avq ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Chaikuad~~, A]]	+	__TOC__
-	[[Category: ~~Routier, S~~]]	+	</StructureSection>
-	[[Category: Knapp, S]]	+	[[Category: Large Structures]]
-	[[Category: ~~Structural Genomics Consortium (Sgc)~~]]	+	[[Category: Chaikuad A]]
		+	[[Category: Knapp S]]
		+	[[Category: Routier S]]

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

2020-11-11T06:20:59Z

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

←Older revision

Revision as of 06:20, 11 November 2020

OCA: New page: '''Unreleased structure''' The entry 7avq is ON HOLD Authors: Chaikuad, A., Routier, S., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of haspin in com...

2020-11-11T06:20:58Z

New page: '''Unreleased structure''' The entry 7avq is ON HOLD Authors: Chaikuad, A., Routier, S., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of haspin in com...

New page

'''Unreleased structure'''

The entry 7avq is ON HOLD

Authors: Chaikuad, A., Routier, S., Knapp, S., Structural Genomics Consortium (SGC)

Description: Crystal structure of haspin in complex with disubstituted imidazo[1,2-b]pyridazine inhibitor (compound 12)
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Routier, S]]
[[Category: Knapp, S]]
[[Category: Structural Genomics Consortium (Sgc)]]