6hjj - Revision history

OCA at 07:21, 31 October 2018

OCA — Wed, 31 Oct 2018 07:21:11 GMT

←Older revision		Revision as of 07:21, 31 October 2018
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	<StructureSection load='6hjj' size='340' side='right' caption='[[6hjj]], [[Resolution\|resolution]] 2.13Å' scene=''>		<StructureSection load='6hjj' size='340' side='right' caption='[[6hjj]], [[Resolution\|resolution]] 2.13Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hjj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HJJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HJJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hjj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HJJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HJJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G7T:~{N}-[4-(4-azanyl-1-propan-2-yl-pyrazolo[3,4-d]pyrimidin-3-yl)-3-methyl-phenyl]-4-[4-fluoranyl-3-(trifluoromethyl)phenyl]-4-oxidanylidene-butanamide'>G7T</scene>, <scene name='pdbligand=PGF:2,5,8,11-TETRAOXATRIDECANE'>PGF</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G7T:~{N}-[4-(4-azanyl-1-propan-2-yl-pyrazolo[3,4-d]pyrimidin-3-yl)-3-methyl-phenyl]-4-[4-fluoranyl-3-(trifluoromethyl)phenyl]-4-oxidanylidene-butanamide'>G7T</scene>, <scene name='pdbligand=PGF:2,5,8,11-TETRAOXATRIDECANE'>PGF</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([http://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'>[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='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=6hjj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hjj OCA], [http://pdbe.org/6hjj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hjj RCSB], [http://www.ebi.ac.uk/pdbsum/6hjj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hjj 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=6hjj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hjj OCA], [http://pdbe.org/6hjj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hjj RCSB], [http://www.ebi.ac.uk/pdbsum/6hjj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hjj ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bayliss, R]]		[[Category: Bayliss, R]]

OCA at 07:54, 3 October 2018

OCA — Wed, 03 Oct 2018 07:54:59 GMT

←Older revision		Revision as of 07:54, 3 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6hjj is ~~ON HOLD~~	+	==Crystal structure of Aurora-A L210C catalytic domain in complex with ASDO6 ligand==
		+	<StructureSection load='6hjj' size='340' side='right' caption='[[6hjj]], [[Resolution\|resolution]] 2.13Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6hjj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HJJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HJJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G7T:~{N}-[4-(4-azanyl-1-propan-2-yl-pyrazolo[3,4-d]pyrimidin-3-yl)-3-methyl-phenyl]-4-[4-fluoranyl-3-(trifluoromethyl)phenyl]-4-oxidanylidene-butanamide'>G7T</scene>, <scene name='pdbligand=PGF:2,5,8,11-TETRAOXATRIDECANE'>PGF</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=6hjj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hjj OCA], [http://pdbe.org/6hjj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hjj RCSB], [http://www.ebi.ac.uk/pdbsum/6hjj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hjj 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 ==
		+	Analog-sensitive (AS) kinases contain large to small mutations in the gatekeeper position rendering them susceptible to inhibition with bulky analogs of pyrazolopyrimidine-based Src kinase inhibitors (e.g. PP1). This 'bump-hole' method has been utilized for at least 85 of ~520 kinases, but many kinases are intolerant to this approach. To expand the scope of AS-kinase technology, we designed type II kinase inhibitors, ASDO2/6 (Analog-Sensitive 'DFG-Out' kinase inhibitors-2/6), that target the 'DFG-out' conformation of cysteine (Cys)-gatekeeper kinases with submicromolar potency. We validated this system in vitro against Greatwall kinase (GWL), Aurora-A kinase and Cyclin-dependent kinase-1 and in cells using M110C-GWL expressing mouse embryonic fibroblasts. These Cys-gatekeeper kinases were sensitive to ASDO2/6-inhibition, but not AS-kinase inhibitor 3MB-PP1 and vice versa. These compounds, with AS-kinase inhibitors, have the potential to inhibit multiple AS-kinases independently with applications in systems level and translational kinase research as well as the rational design of type II kinase inhibitors targeting endogenous kinases.

-	~~Authors: Bayliss, R~~., McIntyre, P.J.	+	Type II kinase inhibitors targeting Cys-gatekeeper kinases display orthogonality with wild type and Ala/Gly-gatekeeper kinases.,Ocasio CA, Warkentin AA, McIntyre PJ, Barkovich KJ, Vesely C, Spencer J, Shokat KM, Bayliss R ACS Chem Biol. 2018 Sep 21. doi: 10.1021/acschembio.8b00592. PMID:30239186<ref>PMID:30239186</ref>

-	~~Description: Crystal structure~~ of ~~Aurora-A L210C catalytic domain in complex with ASDO6 ligand~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Mcintyre, P.J~~]]	+	<div class="pdbe-citations 6hjj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bayliss, R]]		[[Category: Bayliss, R]]
		+	[[Category: McIntyre, P J]]
		+	[[Category: Mitosis]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase]]

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

OCA — Wed, 12 Sep 2018 06:04:11 GMT

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

←Older revision

Revision as of 06:04, 12 September 2018

OCA: New page: '''Unreleased structure''' The entry 6hjj is ON HOLD Authors: Bayliss, R., McIntyre, P.J. Description: Crystal structure of Aurora-A L210C catalytic domain in complex with ASDO6 ligand...

OCA — Wed, 12 Sep 2018 06:04:09 GMT

New page: '''Unreleased structure''' The entry 6hjj is ON HOLD Authors: Bayliss, R., McIntyre, P.J. Description: Crystal structure of Aurora-A L210C catalytic domain in complex with ASDO6 ligand...

New page

'''Unreleased structure'''

The entry 6hjj is ON HOLD

Authors: Bayliss, R., McIntyre, P.J.

Description: Crystal structure of Aurora-A L210C catalytic domain in complex with ASDO6 ligand
[[Category: Unreleased Structures]]
[[Category: Mcintyre, P.J]]
[[Category: Bayliss, R]]