4zs0 - Revision history

OCA at 11:00, 10 January 2024

OCA — Wed, 10 Jan 2024 11:00:56 GMT

←Older revision		Revision as of 11:00, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4zs0]] 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=4ZS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZS0 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4zs0]] 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=4ZS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZS0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4QV:5-HYDROXY-1H-1,2-BIBENZIMIDAZOL-2(3H)-ONE'>4QV</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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4QV:5-HYDROXY-1H-1,2-BIBENZIMIDAZOL-2(3H)-ONE'>4QV</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=4zs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zs0 OCA], [https://pdbe.org/4zs0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zs0 RCSB], [https://www.ebi.ac.uk/pdbsum/4zs0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zs0 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=4zs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zs0 OCA], [https://pdbe.org/4zs0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zs0 RCSB], [https://www.ebi.ac.uk/pdbsum/4zs0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zs0 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:39, 18 May 2023

OCA — Thu, 18 May 2023 07:39:29 GMT

←Older revision		Revision as of 07:39, 18 May 2023
Line 3:		Line 3:
	<StructureSection load='4zs0' size='340' side='right'caption='[[4zs0]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='4zs0' size='340' side='right'caption='[[4zs0]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zs0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZS0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ZS0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zs0]] 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=4ZS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZS0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4QV:5-HYDROXY-1H-1,2-BIBENZIMIDAZOL-2(3H)-ONE'>4QV</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4QV:5-HYDROXY-1H-1,2-BIBENZIMIDAZOL-2(3H)-ONE'>4QV</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://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=4zs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zs0 OCA], [https://pdbe.org/4zs0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zs0 RCSB], [https://www.ebi.ac.uk/pdbsum/4zs0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zs0 ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4zs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zs0 OCA], [~~http~~://pdbe.org/4zs0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4zs0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4zs0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4zs0 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>	+	[https://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4zs0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4zs0" 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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Kilchmann F]]
-	[[Category: Kilchmann, F]]	+	[[Category: Marcaida MJ]]
-	[[Category: Marcaida~~, M J~~]]	+	[[Category: Reymond JL]]
-	[[Category: Reymond~~, J L~~]]	+	[[Category: Schick T]]
-	[[Category: Schick, T]]	+
-	~~[[Category: Aurora]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:17, 10 July 2019

OCA — Wed, 10 Jul 2019 07:17:31 GMT

←Older revision		Revision as of 07:17, 10 July 2019
Line 1:		Line 1:

	==Human Aurora A catalytic domain bound to SB-6-OH==		==Human Aurora A catalytic domain bound to SB-6-OH==
-	<StructureSection load='4zs0' size='340' side='right' caption='[[4zs0]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='4zs0' size='340' side='right'caption='[[4zs0]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4zs0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZS0 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4zs0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZS0 FirstGlance]. <br>
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Kilchmann, F]]		[[Category: Kilchmann, F]]

OCA at 15:14, 26 July 2016

OCA — Tue, 26 Jul 2016 15:14:47 GMT

←Older revision		Revision as of 15:14, 26 July 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 4zs0 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human Aurora A catalytic domain bound to SB-6-OH==
		+	<StructureSection load='4zs0' size='340' side='right' caption='[[4zs0]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4zs0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZS0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4QV:5-HYDROXY-1H-1,2-BIBENZIMIDAZOL-2(3H)-ONE'>4QV</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zs0 OCA], [http://pdbe.org/4zs0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zs0 RCSB], [http://www.ebi.ac.uk/pdbsum/4zs0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zs0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Here we report the discovery of a selective inhibitor of Aurora A, a key regulator of cell division and potential anticancer target. We used the atom category extended ligand overlap score (xLOS), a 3D ligand-based virtual screening method recently developed in our group, to select 437 shape and pharmacophore analogs of reference kinase inhibitors. Biochemical screening uncovered two inhibitor series with scaffolds unprecedented among kinase inhibitors. One of them was successfully optimized by structure-based design to a potent Aurora A inhibitor (IC50 = 2 nM) with very high kinome selectivity for Aurora kinases. This inhibitor locks Aurora A in an inactive conformation and disrupts binding to its activator protein TPX2, which impairs Aurora A localization at the mitotic spindle and induces cell division defects. This phenotype can be rescued by inhibitor-resistant Aurora A mutants. The inhibitor furthermore does not induce Aurora B specific effects in cells.

-	~~Authors: Marcaida, M.J~~., Kilchmann, F., Schick, T., Reymond, J.L.	+	Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening.,Kilchmann F, Marcaida MJ, Kotak S, Schick T, Boss SD, Awale M, Gonczy P, Reymond JL J Med Chem. 2016 Jul 20. PMID:27391133<ref>PMID:27391133</ref>

-	~~Description: Human Aurora A catalytic domain bound to SB~~-6-OH	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Reymond, J.L~~]]	+	<div class="pdbe-citations 4zs0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Kilchmann, F]]		[[Category: Kilchmann, F]]
-	[[Category: Marcaida, M.J]]	+	[[Category: Marcaida, M J]]
		+	[[Category: Reymond, J L]]
	[[Category: Schick, T]]		[[Category: Schick, T]]
		+	[[Category: Aurora]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase]]

OCA: Protected "4zs0" [edit=sysop:move=sysop]

OCA — Wed, 20 May 2015 11:05:29 GMT

Protected "4zs0" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:05, 20 May 2015

OCA: New page: '''Unreleased structure''' The entry 4zs0 is ON HOLD until Paper Publication Authors: Marcaida, M.J., Kilchmann, F., Schick, T., Reymond, J.L. Description: Human Aurora A catalytic dom...

OCA — Wed, 20 May 2015 11:05:28 GMT

New page: '''Unreleased structure''' The entry 4zs0 is ON HOLD until Paper Publication Authors: Marcaida, M.J., Kilchmann, F., Schick, T., Reymond, J.L. Description: Human Aurora A catalytic dom...

New page

'''Unreleased structure'''

The entry 4zs0 is ON HOLD until Paper Publication

Authors: Marcaida, M.J., Kilchmann, F., Schick, T., Reymond, J.L.

Description: Human Aurora A catalytic domain bound to SB-6-OH
[[Category: Unreleased Structures]]
[[Category: Reymond, J.L]]
[[Category: Kilchmann, F]]
[[Category: Marcaida, M.J]]
[[Category: Schick, T]]