4jbp - Revision history

OCA at 08:53, 20 March 2024

OCA — Wed, 20 Mar 2024 08:53:46 GMT

←Older revision		Revision as of 08:53, 20 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4jbp]] 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=4JBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JBP FirstGlance]. <br>		<table><tr><td colspan='2'>[[4jbp]] 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=4JBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JBP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YPH:1-(4-{2-[(6-{4-[2-(4-HYDROXYPIPERIDIN-1-YL)ETHOXY]PHENYL}FURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHYL}PHENYL)-3-PHENYLUREA'>YPH</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]] 2.45Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YPH:1-(4-{2-[(6-{4-[2-(4-HYDROXYPIPERIDIN-1-YL)ETHOXY]PHENYL}FURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHYL}PHENYL)-3-PHENYLUREA'>YPH</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=4jbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jbp OCA], [https://pdbe.org/4jbp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jbp RCSB], [https://www.ebi.ac.uk/pdbsum/4jbp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jbp 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=4jbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jbp OCA], [https://pdbe.org/4jbp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jbp RCSB], [https://www.ebi.ac.uk/pdbsum/4jbp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jbp 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 ==
-	The overexpression of Aurora kinases in multiple tumors makes these kinases appealing targets for the development of anticancer therapies. This study identified two small molecules with a furanopyrimidine core, IBPR001 and IBPR002, that target Aurora kinases and induce a DFG conformation change at the ATP site of Aurora A. Our results demonstrate the high potency of the IBPR compounds in reducing tumorigenesis in a colorectal cancer xenograft model in athymic nude mice. Human hepatoma up-regulated protein (HURP) is a substrate of Aurora kinase A, which plays a crucial role in the stabilization of kinetochore fibers. This study used the IBPR compounds as well as MLN8237, a proven Aurora A inhibitor, as chemical probes to investigate the molecular role of HURP in mitotic spindle formation. These compounds effectively eliminated HURP phosphorylation, thereby revealing the coexistence and continuous cycling of HURP between unphosphorylated and phosphorylated forms that are associated, respectively, with microtubules emanating from centrosomes and kinetochores. Furthermore, these compounds demonstrate a spatial hierarchical preference for HURP in the attachment of microtubules extending from the mother to the daughter centrosome. The finding of inequality in the centrosomal microtubules revealed by these small molecules provides a versatile tool for the discovery of new cell-division molecules for the development of antitumor drugs.
-
-	Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules.,Wu JM, Chen CT, Coumar MS, Lin WH, Chen ZJ, Hsu JT, Peng YH, Shiao HY, Lin WH, Chu CY, Wu JS, Lin CT, Chen CP, Hsueh CC, Chang KY, Kao LP, Huang CY, Chao YS, Wu SY, Hsieh HP, Chi YH Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1779-87. doi:, 10.1073/pnas.1220523110. Epub 2013 Apr 22. PMID:23610398<ref>PMID:23610398</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4jbp" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 11:03, 24 November 2022

OCA — Thu, 24 Nov 2022 11:03:56 GMT

←Older revision		Revision as of 11:03, 24 November 2022
Line 1:		Line 1:

	==Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules==		==Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules==
-	<StructureSection load='4jbp' size='340' side='right' caption='[[4jbp]], [[Resolution\|resolution]] 2.45Å' scene=''>	+	<StructureSection load='4jbp' size='340' side='right'caption='[[4jbp]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4jbp]] 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=4JBP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4JBP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4jbp]] 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=4JBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JBP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YPH:1-(4-{2-[(6-{4-[2-(4-HYDROXYPIPERIDIN-1-YL)ETHOXY]PHENYL}FURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHYL}PHENYL)-3-PHENYLUREA'>YPH</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YPH:1-(4-{2-[(6-{4-[2-(4-HYDROXYPIPERIDIN-1-YL)ETHOXY]PHENYL}FURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHYL}PHENYL)-3-PHENYLUREA'>YPH</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3m11\|3m11]], [[3k5u\|3k5u]], [[4jbo\|4jbo]], [[4jbq\|4jbq]]</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=4jbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jbp OCA], [https://pdbe.org/4jbp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jbp RCSB], [https://www.ebi.ac.uk/pdbsum/4jbp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jbp ProSAT]</span></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='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=4jbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jbp OCA], [~~http~~://pdbe.org/4jbp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4jbp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4jbp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4jbp 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 20:

	==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/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Hsieh~~, H P~~]]	+	[[Category: Hsieh HP]]
-	[[Category: Hsueh~~, C C~~]]	+	[[Category: Hsueh CC]]
-	[[Category: Leou~~, J S~~]]	+	[[Category: Leou JS]]
-	[[Category: Peng~~, Y H~~]]	+	[[Category: Peng YH]]
-	[[Category: Wu~~, J S~~]]	+	[[Category: Wu JS]]
-	[[Category: Wu~~, S Y]]~~	+	[[Category: Wu SY]]
-	~~[[Category: Aurora kinase inhibitor]]~~	+
-	~~[[Category: Hurp]]~~	+
-	~~[[Category: Mitotic spindle]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 12:38, 4 August 2016

OCA — Thu, 04 Aug 2016 12:38:13 GMT

←Older revision		Revision as of 12:38, 4 August 2016
Line 1:		Line 1:
		+
	==Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules==		==Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules==
	<StructureSection load='4jbp' size='340' side='right' caption='[[4jbp]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='4jbp' size='340' side='right' caption='[[4jbp]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4jbp]] is a 1 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=4JBP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JBP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4jbp]] 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=4JBP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JBP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YPH:1-(4-{2-[(6-{4-[2-(4-HYDROXYPIPERIDIN-1-YL)ETHOXY]PHENYL}FURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHYL}PHENYL)-3-PHENYLUREA'>YPH</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YPH:1-(4-{2-[(6-{4-[2-(4-HYDROXYPIPERIDIN-1-YL)ETHOXY]PHENYL}FURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHYL}PHENYL)-3-PHENYLUREA'>YPH</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3m11\|3m11]], [[3k5u\|3k5u]], [[4jbo\|4jbo]], [[4jbq\|4jbq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3m11\|3m11]], [[3k5u\|3k5u]], [[4jbo\|4jbo]], [[4jbq\|4jbq]]</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=4jbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jbp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jbp RCSB], [http://www.ebi.ac.uk/pdbsum/4jbp 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=4jbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jbp OCA], [http://pdbe.org/4jbp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jbp RCSB], [http://www.ebi.ac.uk/pdbsum/4jbp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jbp 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 4jbp" 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: Hsieh, H P]]		[[Category: Hsieh, H P]]

OCA at 14:35, 24 December 2014

OCA — Wed, 24 Dec 2014 14:35:55 GMT

←Older revision		Revision as of 14:35, 24 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4jbp\| PDB=4jbp \| SCENE= }}~~	+	==Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules==
-	===Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules===	+	<StructureSection load='4jbp' size='340' side='right' caption='[[4jbp]], [[Resolution\|resolution]] 2.45Å' scene=''>
-	{{~~ABSTRACT_PUBMED_23610398~~}}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4jbp]] is a 1 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=4JBP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JBP FirstGlance]. <br>
-	==Function==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YPH:1-(4-{2-[(6-{4-[2-(4-HYDROXYPIPERIDIN-1-YL)ETHOXY]PHENYL}FURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHYL}PHENYL)-3-PHENYLUREA'>YPH</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3m11\|3m11]], [[3k5u\|3k5u]], [[4jbo\|4jbo]], [[4jbq\|4jbq]]</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='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=4jbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jbp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jbp RCSB], [http://www.ebi.ac.uk/pdbsum/4jbp PDBsum]</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>		[[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 ==
		+	The overexpression of Aurora kinases in multiple tumors makes these kinases appealing targets for the development of anticancer therapies. This study identified two small molecules with a furanopyrimidine core, IBPR001 and IBPR002, that target Aurora kinases and induce a DFG conformation change at the ATP site of Aurora A. Our results demonstrate the high potency of the IBPR compounds in reducing tumorigenesis in a colorectal cancer xenograft model in athymic nude mice. Human hepatoma up-regulated protein (HURP) is a substrate of Aurora kinase A, which plays a crucial role in the stabilization of kinetochore fibers. This study used the IBPR compounds as well as MLN8237, a proven Aurora A inhibitor, as chemical probes to investigate the molecular role of HURP in mitotic spindle formation. These compounds effectively eliminated HURP phosphorylation, thereby revealing the coexistence and continuous cycling of HURP between unphosphorylated and phosphorylated forms that are associated, respectively, with microtubules emanating from centrosomes and kinetochores. Furthermore, these compounds demonstrate a spatial hierarchical preference for HURP in the attachment of microtubules extending from the mother to the daughter centrosome. The finding of inequality in the centrosomal microtubules revealed by these small molecules provides a versatile tool for the discovery of new cell-division molecules for the development of antitumor drugs.
		+
		+	Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules.,Wu JM, Chen CT, Coumar MS, Lin WH, Chen ZJ, Hsu JT, Peng YH, Shiao HY, Lin WH, Chu CY, Wu JS, Lin CT, Chen CP, Hsueh CC, Chang KY, Kao LP, Huang CY, Chao YS, Wu SY, Hsieh HP, Chi YH Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1779-87. doi:, 10.1073/pnas.1220523110. Epub 2013 Apr 22. PMID:23610398<ref>PMID:23610398</ref>

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4jbp]] is~~ a ~~1 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=4JBP OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023610398</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Hsieh, H P.]]	+	[[Category: Hsieh, H P]]
-	[[Category: Hsueh, C C.]]	+	[[Category: Hsueh, C C]]
-	[[Category: Leou, J S.]]	+	[[Category: Leou, J S]]
-	[[Category: Peng, Y H.]]	+	[[Category: Peng, Y H]]
-	[[Category: Wu, J S.]]	+	[[Category: Wu, J S]]
-	[[Category: Wu, S Y.]]	+	[[Category: Wu, S Y]]
	[[Category: Aurora kinase inhibitor]]		[[Category: Aurora kinase inhibitor]]
	[[Category: Hurp]]		[[Category: Hurp]]
	[[Category: Mitotic spindle]]		[[Category: Mitotic spindle]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 14:03, 19 June 2013

OCA — Wed, 19 Jun 2013 14:03:20 GMT

←Older revision		Revision as of 14:03, 19 June 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4jbp\| PDB=4jbp \| SCENE= }}
		+	===Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules===
		+	{{ABSTRACT_PUBMED_23610398}}

-	~~The entry 4jbp is ON HOLD~~ ~~until Feb 20 2015~~	+	==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>

-	~~Authors~~: ~~Wu, J~~.S.~~, Leou, J~~.~~S., Peng, Y.H., Hsueh, C.C., Hsieh, H~~.P.~~, Wu, S~~.Y.	+	==About this Structure==
		+	[[4jbp]] is a 1 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=4JBP OCA].

-	~~Description~~: ~~Novel~~ Aurora kinase ~~inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules~~	+	==Reference==
		+	<ref group="xtra">PMID:023610398</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Hsieh, H P.]]
		+	[[Category: Hsueh, C C.]]
		+	[[Category: Leou, J S.]]
		+	[[Category: Peng, Y H.]]
		+	[[Category: Wu, J S.]]
		+	[[Category: Wu, S Y.]]
		+	[[Category: Aurora kinase inhibitor]]
		+	[[Category: Hurp]]
		+	[[Category: Mitotic spindle]]
		+	[[Category: Transferase]]

OCA at 16:17, 20 March 2013

OCA — Wed, 20 Mar 2013 16:17:35 GMT

←Older revision		Revision as of 16:17, 20 March 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4jbp is ON HOLD	+	The entry 4jbp is ON HOLD until Feb 20 2015

	Authors: Wu, J.S., Leou, J.S., Peng, Y.H., Hsueh, C.C., Hsieh, H.P., Wu, S.Y.		Authors: Wu, J.S., Leou, J.S., Peng, Y.H., Hsueh, C.C., Hsieh, H.P., Wu, S.Y.

	Description: Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules		Description: Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules

OCA at 13:51, 6 March 2013

OCA — Wed, 06 Mar 2013 13:51:42 GMT

←Older revision		Revision as of 13:51, 6 March 2013
Line 3:		Line 3:
	The entry 4jbp is ON HOLD		The entry 4jbp is ON HOLD

-	Authors: Wu, J.S., Leou, J.S, Peng, Y.H., Hsueh, C.C., Hsieh, H.P., Wu, S.Y.	+	Authors: Wu, J.S., Leou, J.S., Peng, Y.H., Hsueh, C.C., Hsieh, H.P., Wu, S.Y.

	Description: Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules		Description: Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules

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

OCA — Wed, 27 Feb 2013 14:28:41 GMT

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

←Older revision

Revision as of 14:28, 27 February 2013

OCA: New page: '''Unreleased structure''' The entry 4jbp is ON HOLD Authors: Wu, J.S., Leou, J.S, Peng, Y.H., Hsueh, C.C., Hsieh, H.P., Wu, S.Y. Description: Novel Aurora kinase inhibitors reveal mec...

OCA — Wed, 27 Feb 2013 14:28:40 GMT

New page: '''Unreleased structure''' The entry 4jbp is ON HOLD Authors: Wu, J.S., Leou, J.S, Peng, Y.H., Hsueh, C.C., Hsieh, H.P., Wu, S.Y. Description: Novel Aurora kinase inhibitors reveal mec...

New page

'''Unreleased structure'''

The entry 4jbp is ON HOLD

Authors: Wu, J.S., Leou, J.S, Peng, Y.H., Hsueh, C.C., Hsieh, H.P., Wu, S.Y.

Description: Novel Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules