7ops - Revision history

OCA at 12:54, 1 February 2024

2024-02-01T12:54:24Z

← Older revision		Revision as of 12:54, 1 February 2024
Line 1:		Line 1:

	==Crystal structure of haspin in complex with ZW282 (compound 2a)==		==Crystal structure of haspin in complex with ZW282 (compound 2a)==
	<StructureSection load='7ops' size='340' side='right'caption='[[7ops]]' scene=''>		<StructureSection load='7ops' size='340' side='right'caption='[[7ops]], [[Resolution\|resolution]] 2.38Å' 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=7OPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ops]] 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=7OPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPS 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=7ops FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ops OCA], [https://pdbe.org/7ops PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ops RCSB], [https://www.ebi.ac.uk/pdbsum/7ops PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ops 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]] 2.38Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=07C:2-methylsulfanyl-10-nitro-pyrido[3,4-g]quinazoline'>07C</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7ops FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ops OCA], [https://pdbe.org/7ops PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ops RCSB], [https://www.ebi.ac.uk/pdbsum/7ops PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ops 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 (haploid germ cell-specific nuclear protein kinase) offers a potential target for the development of new anticancer drugs. Thus, the identification of new inhibitors targeting this protein kinase is of high interest. However, Haspin inhibitors developed to date show a poor selectivity profile over other protein kinases of the human kinome. Here, we identified a new pyridoquinazoline based inhibitor (4), with excellent inhibitory activity and selectivity for Haspin (IC50 of 50 nM). We describe the structure-activity relationship study including the evaluation of this inhibitor on a large panel of 486 kinases as well as on immortalized or cancer cell lines. In addition, we determined the binding mode of analog 2a in complex with Haspin using X-ray crystallography.

			Synthesis and biological evaluation of Haspin inhibitors: Kinase inhibitory potency and cellular activity.,Zeinyeh W, Esvan YJ, Josselin B, Defois M, Baratte B, Knapp S, Chaikuad A, Anizon F, Giraud F, Ruchaud S, Moreau P Eur J Med Chem. 2022 Apr 9;236:114369. doi: 10.1016/j.ejmech.2022.114369. PMID:35447555<ref>PMID:35447555</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7ops" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Anizon F]]		[[Category: Anizon F]]
	[[Category: Chaikuad A]]		[[Category: Chaikuad A]]
	[[Category: Knapp S]]		[[Category: Knapp S]]

OCA at 14:47, 31 August 2022

2022-08-31T14:47:21Z

← Older revision		Revision as of 14:47, 31 August 2022
Line 1:		Line 1:

	==Crystal structure of haspin in complex with ZW282 (compound 2a)==		==Crystal structure of haspin in complex with ZW282 (compound 2a)==
	<StructureSection load='7ops' size='340' side='right'caption='[[7ops]]~~, [[Resolution\|resolution]] 2.38Å~~' scene=''>		<StructureSection load='7ops' size='340' side='right'caption='[[7ops]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[7ops]] 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=7OPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPS FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=07C:2-methylsulfanyl-10-nitro-pyrido[3,4-g]quinazoline'>07C</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</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=7ops FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ops OCA], [https://pdbe.org/7ops PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ops RCSB], [https://www.ebi.ac.uk/pdbsum/7ops PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ops ProSAT]</span></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=7ops FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ops OCA], [https://pdbe.org/7ops PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ops RCSB], [https://www.ebi.ac.uk/pdbsum/7ops PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ops 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 (haploid germ cell-specific nuclear protein kinase) offers a potential target for the development of new anticancer drugs. Thus, the identification of new inhibitors targeting this protein kinase is of high interest. However, Haspin inhibitors developed to date show a poor selectivity profile over other protein kinases of the human kinome. Here, we identified a new pyridoquinazoline based inhibitor (4), with excellent inhibitory activity and selectivity for Haspin (IC50 of 50 nM). We describe the structure-activity relationship study including the evaluation of this inhibitor on a large panel of 486 kinases as well as on immortalized or cancer cell lines. In addition, we determined the binding mode of analog 2a in complex with Haspin using X-ray crystallography.

	Synthesis and biological evaluation of Haspin inhibitors: Kinase inhibitory potency and cellular activity.,Zeinyeh W, Esvan YJ, Josselin B, Defois M, Baratte B, Knapp S, Chaikuad A, Anizon F, Giraud F, Ruchaud S, Moreau P Eur J Med Chem. 2022 Apr 9;236:114369. doi: 10.1016/j.ejmech.2022.114369. PMID:35447555<ref>PMID:35447555</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 7ops" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Human]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific serine/threonine protein kinase]]~~		[[Category: Anizon F]]
	[[Category: Anizon, F]]		[[Category: Chaikuad A]]
	[[Category: Chaikuad, A]]		[[Category: Knapp S]]
	[[Category: Knapp, S]]
	~~[[Category: Structural genomic]]~~
	~~[[Category: Gsg2]]~~
	~~[[Category: Haspin]]~~
	~~[[Category: Kinase inhibitor]]~~
	~~[[Category: Sgc]]~~
	~~[[Category: Transferase~~]]

OCA at 06:30, 12 May 2022

2022-05-12T06:30:17Z

← Older revision		Revision as of 06:30, 12 May 2022
Line 1:		Line 1:

	==Crystal structure of haspin in complex with ZW282 (compound 2a)==		==Crystal structure of haspin in complex with ZW282 (compound 2a)==
	<StructureSection load='7ops' size='340' side='right'caption='[[7ops]]' scene=''>		<StructureSection load='7ops' size='340' side='right'caption='[[7ops]], [[Resolution\|resolution]] 2.38Å' 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=7OPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ops]] 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=7OPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPS 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=7ops FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ops OCA], [https://pdbe.org/7ops PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ops RCSB], [https://www.ebi.ac.uk/pdbsum/7ops PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ops 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=07C:2-methylsulfanyl-10-nitro-pyrido[3,4-g]quinazoline'>07C</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7ops FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ops OCA], [https://pdbe.org/7ops PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ops RCSB], [https://www.ebi.ac.uk/pdbsum/7ops PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ops 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 (haploid germ cell-specific nuclear protein kinase) offers a potential target for the development of new anticancer drugs. Thus, the identification of new inhibitors targeting this protein kinase is of high interest. However, Haspin inhibitors developed to date show a poor selectivity profile over other protein kinases of the human kinome. Here, we identified a new pyridoquinazoline based inhibitor (4), with excellent inhibitory activity and selectivity for Haspin (IC50 of 50 nM). We describe the structure-activity relationship study including the evaluation of this inhibitor on a large panel of 486 kinases as well as on immortalized or cancer cell lines. In addition, we determined the binding mode of analog 2a in complex with Haspin using X-ray crystallography.

			Synthesis and biological evaluation of Haspin inhibitors: Kinase inhibitory potency and cellular activity.,Zeinyeh W, Esvan YJ, Josselin B, Defois M, Baratte B, Knapp S, Chaikuad A, Anizon F, Giraud F, Ruchaud S, Moreau P Eur J Med Chem. 2022 Apr 9;236:114369. doi: 10.1016/j.ejmech.2022.114369. PMID:35447555<ref>PMID:35447555</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7ops" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Anizon F]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Chaikuad A]]		[[Category: Anizon, F]]
	[[Category: Knapp S]]		[[Category: Chaikuad, A]]
			[[Category: Knapp, S]]
			[[Category: Structural genomic]]
			[[Category: Gsg2]]
			[[Category: Haspin]]
			[[Category: Kinase inhibitor]]
			[[Category: Sgc]]
			[[Category: Transferase]]

OCA at 09:00, 21 July 2021

2021-07-21T09:00:01Z

← Older revision		Revision as of 09:00, 21 July 2021
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry 7ops is ON HOLD~~		==Crystal structure of haspin in complex with ZW282 (compound 2a)==
			<StructureSection load='7ops' size='340' side='right'caption='[[7ops]]' scene=''>
	~~Authors: Chaikuad, A., Anizon, F., 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=7OPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OPS FirstGlance]. <br>
	~~Description:~~ Crystal structure of haspin in complex with ZW282 (compound 2a)		</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=7ops FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ops OCA], [https://pdbe.org/7ops PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ops RCSB], [https://www.ebi.ac.uk/pdbsum/7ops PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ops ProSAT]</span></td></tr>
	[[~~Category~~: ~~Unreleased Structures~~]]		</table>
	[[~~Category~~: ~~Chaikuad~~, A]]		__TOC__
	[[Category: ~~Knapp, S~~]]		</StructureSection>
	[[Category: Anizon, F]]		[[Category: Large Structures]]
	[[Category: ~~Structural Genomics Consortium (Sgc)~~]]		[[Category: Anizon F]]
			[[Category: Chaikuad A]]
			[[Category: Knapp S]]

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

2021-06-09T11:15:17Z

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

← Older revision	Revision as of 11:15, 9 June 2021
(No difference)

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

2021-06-09T11:15:16Z

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

New page

'''Unreleased structure'''

The entry 7ops is ON HOLD

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

Description: Crystal structure of haspin in complex with ZW282 (compound 2a)
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Knapp, S]]
[[Category: Anizon, F]]
[[Category: Structural Genomics Consortium (Sgc)]]