3uoh - Revision history

OCA at 14:03, 14 March 2024

2024-03-14T14:03:59Z

← Older revision		Revision as of 14:03, 14 March 2024
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	<StructureSection load='3uoh' size='340' side='right'caption='[[3uoh]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3uoh' size='340' side='right'caption='[[3uoh]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3uoh]] is a 2 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=3UOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UOH FirstGlance]. <br>		<table><tr><td colspan='2'>[[3uoh]] is a 2 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=3UOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UOH FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=0C4:4-({4~~-[~~(2-BROMOPHENYL)AMINO~~]~~PYRIMIDIN-~~2~~-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.8002Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style~~='overflow: auto; max-height: 3em;'>[[3unj\|3unj]], [[3unk\|3unk]], [[3unz\|3unz]], [[3uo4\|3uo4]], [[3uo5\|3uo5]], [[3uo6\|3uo6]], [[3uod\|3uod]], [[3uoj\|3uoj]], [[3uok\|3uok]], [[3uol\|3uol]], [[3up2\|3up2]], [[3up7\|3up7]]</div><~~/td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0C4:4-({4-[(2-BROMOPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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~~ ([~~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=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [https://pdbe.org/3uoh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [https://www.ebi.ac.uk/pdbsum/3uoh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uoh 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=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [https://pdbe.org/3uoh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [https://www.ebi.ac.uk/pdbsum/3uoh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uoh ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[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>		[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;">~~
	~~== Publication Abstract from PubMed ==~~
	Most protein kinases share a DFG (Asp-Phe-Gly) motif in the ATP site which can assume two distinct conformations, the active DFG-in and the inactive DFG-out states. Small molecule inhibitors able to induce the DFG-out state have received considerable attention in kinase drug discovery. Using a typical DFG-in inhibitor scaffold of Aurora A, a kinase involved in the regulation of cell division, we found that halogen and nitrile substituents directed at the N-terminally flanking residue Ala273 induced global conformational changes in the enzyme, leading to DFG-out inhibitors that are among the most potent Aurora A inhibitors reported to date. The data suggest an unprecedented mechanism of action, in which induced-dipole forces along the Ala273 side chain alter the charge distribution of the DFG backbone, allowing the DFG to unwind. As the ADFG sequence and three-dimensional structure is highly conserved, DFG-out inhibitors of other kinases may be designed by specifically targeting the flanking alanine residue with electric dipoles.

	A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A.,Martin MP, Zhu JY, Lawrence H, Pireddu R, Luo Y, Alam R, Ozcan S, Sebti SM, Lawrence NJ, Schonbrunn E ACS Chem Biol. 2012 Jan 16. PMID:22248356<ref>PMID:22248356</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3uoh" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==
Line 28:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific serine/threonine protein kinase]]~~		[[Category: Martin MP]]
	[[Category: Martin~~, M P~~]]		[[Category: Schonbrunn E]]
	[[Category: Schonbrunn, E]]		[[Category: Zhu J-Y]]
	[[Category: Zhu, J Y]]
	~~[[Category: Aurora some]]~~
	~~[[Category: Dfg-out]]~~
	~~[[Category: Inhibitor]]~~
	~~[[Category: Protein kinase]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 07:53, 20 July 2022

2022-07-20T07:53:15Z

← Older revision		Revision as of 07:53, 20 July 2022
Line 1:		Line 1:

	==Aurora A in complex with RPM1722==		==Aurora A in complex with RPM1722==
	<StructureSection load='3uoh' size='340' side='right' caption='[[3uoh]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3uoh' size='340' side='right'caption='[[3uoh]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3uoh]] is a 2 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=3UOH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3UOH FirstGlance]. <br>		<table><tr><td colspan='2'>[[3uoh]] is a 2 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=3UOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UOH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0C4:4-({4-[(2-BROMOPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0C4:4-({4-[(2-BROMOPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3unj\|3unj]], [[3unk\|3unk]], [[3unz\|3unz]], [[3uo4\|3uo4]], [[3uo5\|3uo5]], [[3uo6\|3uo6]], [[3uod\|3uod]], [[3uoj\|3uoj]], [[3uok\|3uok]], [[3uol\|3uol]], [[3up2\|3up2]], [[3up7\|3up7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3unj\|3unj]], [[3unk\|3unk]], [[3unz\|3unz]], [[3uo4\|3uo4]], [[3uo5\|3uo5]], [[3uo6\|3uo6]], [[3uod\|3uod]], [[3uoj\|3uoj]], [[3uok\|3uok]], [[3uol\|3uol]], [[3up2\|3up2]], [[3up7\|3up7]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([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'>[~~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'>[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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [~~http~~://pdbe.org/3uoh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3uoh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3uoh 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=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [https://pdbe.org/3uoh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [https://www.ebi.ac.uk/pdbsum/3uoh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uoh 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 23:		Line 23:

	==See Also==		==See Also==
	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Martin, M P]]		[[Category: Martin, M P]]

OCA at 12:40, 4 August 2016

2016-08-04T12:40:58Z

← Older revision		Revision as of 12:40, 4 August 2016
Line 1:		Line 1:

	==Aurora A in complex with RPM1722==		==Aurora A in complex with RPM1722==
	<StructureSection load='3uoh' size='340' side='right' caption='[[3uoh]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3uoh' size='340' side='right' caption='[[3uoh]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3uoh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UOH FirstGlance]. <br>		<table><tr><td colspan='2'>[[3uoh]] is a 2 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=3UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UOH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0C4:4-({4-[(2-BROMOPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0C4:4-({4-[(2-BROMOPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3unj\|3unj]], [[3unk\|3unk]], [[3unz\|3unz]], [[3uo4\|3uo4]], [[3uo5\|3uo5]], [[3uo6\|3uo6]], [[3uod\|3uod]], [[3uoj\|3uoj]], [[3uok\|3uok]], [[3uol\|3uol]], [[3up2\|3up2]], [[3up7\|3up7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3unj\|3unj]], [[3unk\|3unk]], [[3unz\|3unz]], [[3uo4\|3uo4]], [[3uo5\|3uo5]], [[3uo6\|3uo6]], [[3uod\|3uod]], [[3uoj\|3uoj]], [[3uok\|3uok]], [[3uol\|3uol]], [[3up2\|3up2]], [[3up7\|3up7]]</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 ~~Homo sapiens~~])</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=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [http://www.ebi.ac.uk/pdbsum/3uoh PDBsum]</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=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [http://pdbe.org/3uoh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [http://www.ebi.ac.uk/pdbsum/3uoh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uoh ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3uoh" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Martin, M P]]		[[Category: Martin, M P]]

OCA at 14:37, 24 December 2014

2014-12-24T14:37:46Z

← Older revision		Revision as of 14:37, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3uoh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UOH FirstGlance]. <br>		<table><tr><td colspan='2'>[[3uoh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UOH FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0C4:4-({4-[(2-BROMOPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0C4:4-({4-[(2-BROMOPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3unj\|3unj]], [[3unk\|3unk]], [[3unz\|3unz]], [[3uo4\|3uo4]], [[3uo5\|3uo5]], [[3uo6\|3uo6]], [[3uod\|3uod]], [[3uoj\|3uoj]], [[3uok\|3uok]], [[3uol\|3uol]], [[3up2\|3up2]], [[3up7\|3up7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3unj\|3unj]], [[3unk\|3unk]], [[3unz\|3unz]], [[3uo4\|3uo4]], [[3uo5\|3uo5]], [[3uo6\|3uo6]], [[3uod\|3uod]], [[3uoj\|3uoj]], [[3uok\|3uok]], [[3uol\|3uol]], [[3up2\|3up2]], [[3up7\|3up7]]</td></tr>
	<tr><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 Homo sapiens])</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 Homo sapiens])</td></tr>
	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [http://www.ebi.ac.uk/pdbsum/3uoh PDBsum]</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=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [http://www.ebi.ac.uk/pdbsum/3uoh PDBsum]</span></td></tr>
	<table>		</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 15:		Line 17:
	A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A.,Martin MP, Zhu JY, Lawrence H, Pireddu R, Luo Y, Alam R, Ozcan S, Sebti SM, Lawrence NJ, Schonbrunn E ACS Chem Biol. 2012 Jan 16. PMID:22248356<ref>PMID:22248356</ref>		A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A.,Martin MP, Zhu JY, Lawrence H, Pireddu R, Luo Y, Alam R, Ozcan S, Sebti SM, Lawrence NJ, Schonbrunn E ACS Chem Biol. 2012 Jan 16. PMID:22248356<ref>PMID:22248356</ref>

	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>

Line 26:		Line 28:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Martin, M P.]]		[[Category: Martin, M P]]
	[[Category: Schonbrunn, E.]]		[[Category: Schonbrunn, E]]
	[[Category: Zhu, J Y.]]		[[Category: Zhu, J Y]]
	[[Category: Aurora some]]		[[Category: Aurora some]]
	[[Category: Dfg-out]]		[[Category: Dfg-out]]

OCA at 06:17, 5 June 2014

2014-06-05T06:17:04Z

← Older revision		Revision as of 06:17, 5 June 2014
Line 1:		Line 1:
	[[~~Image~~:~~3uoh~~.~~png~~\|~~left~~\|~~200px~~]]		==Aurora A in complex with RPM1722==
			<StructureSection load='3uoh' size='340' side='right' caption='[[3uoh]], [[Resolution\|resolution]] 2.80Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[3uoh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UOH FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0C4:4-({4-[(2-BROMOPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZOIC+ACID'>0C4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3unj\|3unj]], [[3unk\|3unk]], [[3unz\|3unz]], [[3uo4\|3uo4]], [[3uo5\|3uo5]], [[3uo6\|3uo6]], [[3uod\|3uod]], [[3uoj\|3uoj]], [[3uok\|3uok]], [[3uol\|3uol]], [[3up2\|3up2]], [[3up7\|3up7]]</td></tr>
			<tr><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 Homo sapiens])</td></tr>
			<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uoh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uoh RCSB], [http://www.ebi.ac.uk/pdbsum/3uoh PDBsum]</span></td></tr>
			<table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Most protein kinases share a DFG (Asp-Phe-Gly) motif in the ATP site which can assume two distinct conformations, the active DFG-in and the inactive DFG-out states. Small molecule inhibitors able to induce the DFG-out state have received considerable attention in kinase drug discovery. Using a typical DFG-in inhibitor scaffold of Aurora A, a kinase involved in the regulation of cell division, we found that halogen and nitrile substituents directed at the N-terminally flanking residue Ala273 induced global conformational changes in the enzyme, leading to DFG-out inhibitors that are among the most potent Aurora A inhibitors reported to date. The data suggest an unprecedented mechanism of action, in which induced-dipole forces along the Ala273 side chain alter the charge distribution of the DFG backbone, allowing the DFG to unwind. As the ADFG sequence and three-dimensional structure is highly conserved, DFG-out inhibitors of other kinases may be designed by specifically targeting the flanking alanine residue with electric dipoles.

	~~<!--~~		A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A.,Martin MP, Zhu JY, Lawrence H, Pireddu R, Luo Y, Alam R, Ozcan S, Sebti SM, Lawrence NJ, Schonbrunn E ACS Chem Biol. 2012 Jan 16. PMID:22248356<ref>PMID:22248356</ref>
	~~The line below this paragraph~~, ~~containing "STRUCTURE_3uoh"~~, ~~creates the "Structure Box" on the page~~.
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display~~.
	-->
	~~{{STRUCTURE_3uoh\| PDB=3uoh \| SCENE= }}~~

	~~===Aurora A in complex with RPM1722===~~		From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
			</div>

			==See Also==
	~~<!--~~		*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22248356}}, adds the Publication Abstract to the page~~		== References ==
	~~(as it appears on PubMed at http://www.pubmed.gov), where 22248356 is the PubMed ID number.~~		<references/>
	~~-->~~		__TOC__
	~~{{ABSTRACT_PUBMED_22248356}}~~		</StructureSection>

	==~~About this Structure~~==
	[[~~3uoh]] is a 2 chain structure with sequence from [http:/~~/~~en.wikipedia.org~~/~~wiki/Homo_sapiens Homo sapiens~~]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UOH OCA~~].

	==~~Reference~~==
	<~~ref group="xtra">PMID:022248356<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 07:30, 1 February 2012

2012-02-01T07:30:38Z

← Older revision		Revision as of 07:30, 1 February 2012
Line 1:		Line 1:
	[[Image:3uoh.~~jpg~~\|left\|200px]]		[[Image:3uoh.png\|left\|200px]]

	<!--		<!--

OCA at 06:26, 25 January 2012

2012-01-25T06:26:10Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:3uoh.jpg|left|200px]]
-The entry 3uoh is ON HOLD
+<!--
-Authors: Martin, M.P., Zhu, J.-Y., Schonbrunn, E.
+===Aurora A in complex with RPM1722===
-Description: Aurora A in complex with RPM1722

OCA at 07:36, 7 December 2011

2011-12-07T07:36:37Z

← Older revision		Revision as of 07:36, 7 December 2011
Line 5:		Line 5:
	Authors: Martin, M.P., Zhu, J.-Y., Schonbrunn, E.		Authors: Martin, M.P., Zhu, J.-Y., Schonbrunn, E.

	Description: ~~AURORA~~ A ~~IN COMPLEX WITH~~ RPM1722		Description: Aurora A in complex with RPM1722

OCA: Protected "3uoh" [edit=sysop:move=sysop]

2011-11-23T18:41:32Z

Protected "3uoh" [edit=sysop:move=sysop]

← Older revision	Revision as of 18:41, 23 November 2011
(No difference)

OCA: New page: '''Unreleased structure''' The entry 3uoh is ON HOLD Authors: Martin, M.P., Zhu, J.-Y., Schonbrunn, E. Description: AURORA A IN COMPLEX WITH RPM1722

2011-11-23T18:41:31Z

New page: '''Unreleased structure''' The entry 3uoh is ON HOLD Authors: Martin, M.P., Zhu, J.-Y., Schonbrunn, E. Description: AURORA A IN COMPLEX WITH RPM1722

New page

'''Unreleased structure'''

The entry 3uoh is ON HOLD

Authors: Martin, M.P., Zhu, J.-Y., Schonbrunn, E.

Description: AURORA A IN COMPLEX WITH RPM1722