4byi - Revision history

OCA at 12:00, 20 December 2023

2023-12-20T12:00:27Z

←Older revision		Revision as of 12:00, 20 December 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4byi]] 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=4BYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BYI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4byi]] 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=4BYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BYI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FH3:(S)-N-((1-(6-CHLORO-2-(1,3-DIMETHYL-1H-PYRAZOL-4-YL)-3H-IMIDAZO[4,5-B]PYRIDIN-7-YL)PYRROLIDIN-3-YL)METHYL)ACETAMIDE'>FH3</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]] 2.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FH3:(S)-N-((1-(6-CHLORO-2-(1,3-DIMETHYL-1H-PYRAZOL-4-YL)-3H-IMIDAZO[4,5-B]PYRIDIN-7-YL)PYRROLIDIN-3-YL)METHYL)ACETAMIDE'>FH3</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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [https://pdbe.org/4byi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [https://www.ebi.ac.uk/pdbsum/4byi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4byi 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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [https://pdbe.org/4byi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [https://www.ebi.ac.uk/pdbsum/4byi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4byi 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 ==
		+	Aurora-A differs from Aurora-B/C at three positions in the ATP-binding pocket (L215, T217, and R220). Exploiting these differences, crystal structures of ligand-Aurora protein interactions formed the basis of a design principle for imidazo[4,5-b]pyridine-derived Aurora-A-selective inhibitors. Guided by a computational modeling approach, appropriate C7-imidazo[4,5-b]pyridine derivatization led to the discovery of highly selective inhibitors, such as compound 28c, of Aurora-A over Aurora-B. In HCT116 human colon carcinoma cells, 28c and 40f inhibited the Aurora-A L215R and R220K mutants with IC50 values similar to those seen for the Aurora-A wild type. However, the Aurora-A T217E mutant was significantly less sensitive to inhibition by 28c and 40f compared to the Aurora-A wild type, suggesting that the T217 residue plays a critical role in governing the observed isoform selectivity for Aurora-A inhibition. These compounds are useful small-molecule chemical tools to further explore the function of Aurora-A in cells.
		+
		+	Aurora Isoform Selectivity: Design and Synthesis of Imidazo[4,5-b]pyridine Derivatives as Highly Selective Inhibitors of Aurora-A Kinase in Cells.,Bavetsias V, Faisal A, Crumpler S, Brown N, Kosmopoulou M, Joshi A, Atrash B, Perez-Fuertes Y, Schmitt JA, Boxall KJ, Burke R, Sun C, Avery S, Bush K, Henley A, Raynaud FI, Workman P, Bayliss R, Linardopoulos S, Blagg J J Med Chem. 2013 Nov 6. PMID:24195668<ref>PMID:24195668</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4byi" style="background-color:#fffaf0;"></div>

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

OCA at 17:16, 7 September 2022

2022-09-07T17:16:24Z

←Older revision		Revision as of 17:16, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4byi' size='340' side='right'caption='[[4byi]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4byi' size='340' side='right'caption='[[4byi]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4byi]] 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=4BYI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BYI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4byi]] 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=4BYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BYI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FH3:(S)-N-((1-(6-CHLORO-2-(1,3-DIMETHYL-1H-PYRAZOL-4-YL)-3H-IMIDAZO[4,5-B]PYRIDIN-7-YL)PYRROLIDIN-3-YL)METHYL)ACETAMIDE'>FH3</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FH3:(S)-N-((1-(6-CHLORO-2-(1,3-DIMETHYL-1H-PYRAZOL-4-YL)-3H-IMIDAZO[4,5-B]PYRIDIN-7-YL)PYRROLIDIN-3-YL)METHYL)ACETAMIDE'>FH3</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4byj\|4byj]]</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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [https://pdbe.org/4byi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [https://www.ebi.ac.uk/pdbsum/4byi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4byi ProSAT]</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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [~~http~~://pdbe.org/4byi PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4byi PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4byi 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Aurora-A differs from Aurora-B/C at three positions in the ATP-binding pocket (L215, T217, and R220). Exploiting these differences, crystal structures of ligand-Aurora protein interactions formed the basis of a design principle for imidazo[4,5-b]pyridine-derived Aurora-A-selective inhibitors. Guided by a computational modeling approach, appropriate C7-imidazo[4,5-b]pyridine derivatization led to the discovery of highly selective inhibitors, such as compound 28c, of Aurora-A over Aurora-B. In HCT116 human colon carcinoma cells, 28c and 40f inhibited the Aurora-A L215R and R220K mutants with IC50 values similar to those seen for the Aurora-A wild type. However, the Aurora-A T217E mutant was significantly less sensitive to inhibition by 28c and 40f compared to the Aurora-A wild type, suggesting that the T217 residue plays a critical role in governing the observed isoform selectivity for Aurora-A inhibition. These compounds are useful small-molecule chemical tools to further explore the function of Aurora-A in cells.	+

-	~~Aurora Isoform Selectivity: Design and Synthesis of Imidazo~~[4,5-b]pyridine Derivatives as Highly Selective Inhibitors of Aurora-A Kinase in Cells.,Bavetsias V, Faisal A, Crumpler S, Brown N, Kosmopoulou M, Joshi A, Atrash B, Perez-Fuertes Y, Schmitt JA, Boxall KJ, Burke R, Sun C, Avery S, Bush K, Henley A, Raynaud FI, Workman P, Bayliss R, Linardopoulos S, Blagg J J Med Chem. 2013 Nov 6. PMID:24195668<ref>PMID:24195668</~~ref>~~	+	==See Also==
-		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
-	~~From MEDLINE®~~/~~PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4byi" style="background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Bayliss R]]
-	[[Category: Bayliss, R]]	+	[[Category: Joshi A]]
-	[[Category: Joshi, A]]	+	[[Category: Kosmopoulou M]]
-	[[Category: Kosmopoulou, M]]	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 13:17, 13 March 2019

2019-03-13T13:17:23Z

←Older revision		Revision as of 13:17, 13 March 2019
Line 1:		Line 1:

	==Aurora A kinase bound to a highly selective imidazopyridine inhibitor==		==Aurora A kinase bound to a highly selective imidazopyridine inhibitor==
-	<StructureSection load='4byi' size='340' side='right' caption='[[4byi]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='4byi' size='340' side='right'caption='[[4byi]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4byi]] 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=4BYI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BYI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4byi]] 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=4BYI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BYI FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4byi" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4byi" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bayliss, R]]		[[Category: Bayliss, R]]

OCA at 21:40, 4 August 2016

2016-08-04T21:40:00Z

←Older revision		Revision as of 21:40, 4 August 2016
Line 1:		Line 1:
		+
	==Aurora A kinase bound to a highly selective imidazopyridine inhibitor==		==Aurora A kinase bound to a highly selective imidazopyridine inhibitor==
	<StructureSection load='4byi' size='340' side='right' caption='[[4byi]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4byi' size='340' side='right' caption='[[4byi]], [[Resolution\|resolution]] 2.60Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4byj\|4byj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4byj\|4byj]]</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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [http://www.ebi.ac.uk/pdbsum/4byi 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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [http://pdbe.org/4byi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [http://www.ebi.ac.uk/pdbsum/4byi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4byi ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4byi" style="background-color:#fffaf0;"></div>

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

OCA at 13:22, 25 December 2014

2014-12-25T13:22:50Z

←Older revision		Revision as of 13:22, 25 December 2014
Line 8:		Line 8:
	<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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [http://www.ebi.ac.uk/pdbsum/4byi 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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [http://www.ebi.ac.uk/pdbsum/4byi 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 ==

OCA at 16:46, 21 December 2014

2014-12-21T16:46:02Z

←Older revision		Revision as of 16:46, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4byi\| PDB=4byi \| SCENE= }}~~	+	==Aurora A kinase bound to a highly selective imidazopyridine inhibitor==
-	===Aurora A kinase bound to a highly selective imidazopyridine inhibitor===	+	<StructureSection load='4byi' size='340' side='right' caption='[[4byi]], [[Resolution\|resolution]] 2.60Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24195668}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4byi]] 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=4BYI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BYI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FH3:(S)-N-((1-(6-CHLORO-2-(1,3-DIMETHYL-1H-PYRAZOL-4-YL)-3H-IMIDAZO[4,5-B]PYRIDIN-7-YL)PYRROLIDIN-3-YL)METHYL)ACETAMIDE'>FH3</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4byj\|4byj]]</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=4byi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4byi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4byi RCSB], [http://www.ebi.ac.uk/pdbsum/4byi PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aurora-A differs from Aurora-B/C at three positions in the ATP-binding pocket (L215, T217, and R220). Exploiting these differences, crystal structures of ligand-Aurora protein interactions formed the basis of a design principle for imidazo[4,5-b]pyridine-derived Aurora-A-selective inhibitors. Guided by a computational modeling approach, appropriate C7-imidazo[4,5-b]pyridine derivatization led to the discovery of highly selective inhibitors, such as compound 28c, of Aurora-A over Aurora-B. In HCT116 human colon carcinoma cells, 28c and 40f inhibited the Aurora-A L215R and R220K mutants with IC50 values similar to those seen for the Aurora-A wild type. However, the Aurora-A T217E mutant was significantly less sensitive to inhibition by 28c and 40f compared to the Aurora-A wild type, suggesting that the T217 residue plays a critical role in governing the observed isoform selectivity for Aurora-A inhibition. These compounds are useful small-molecule chemical tools to further explore the function of Aurora-A in cells.

-	~~==Function==~~	+	Aurora Isoform Selectivity: Design and Synthesis of Imidazo[4,5-b]pyridine Derivatives as Highly Selective Inhibitors of Aurora-A Kinase in Cells.,Bavetsias V, Faisal A, Crumpler S, Brown N, Kosmopoulou M, Joshi A, Atrash B, Perez-Fuertes Y, Schmitt JA, Boxall KJ, Burke R, Sun C, Avery S, Bush K, Henley A, Raynaud FI, Workman P, Bayliss R, Linardopoulos S, Blagg J J Med Chem. 2013 Nov 6. PMID:24195668<ref>PMID:24195668</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>	+

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

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:024195668</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Bayliss, R.]]	+	[[Category: Bayliss, R]]
-	[[Category: Joshi, A.]]	+	[[Category: Joshi, A]]
-	[[Category: Kosmopoulou, M.]]	+	[[Category: Kosmopoulou, M]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 12:24, 11 December 2013

2013-12-11T12:24:28Z

←Older revision		Revision as of 12:24, 11 December 2013
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
-	[[4byi]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BYI OCA].	+	[[4byi]] 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=4BYI OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:024195668</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:024195668</ref><references group="xtra"/><references/>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bayliss, R.]]		[[Category: Bayliss, R.]]

OCA at 13:31, 20 November 2013

2013-11-20T13:31:39Z

←Older revision		Revision as of 13:31, 20 November 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4byi\| PDB=4byi \| SCENE= }}
		+	===Aurora A kinase bound to a highly selective imidazopyridine inhibitor===
		+	{{ABSTRACT_PUBMED_24195668}}

-	~~The entry 4byi is ON HOLD~~ ~~until Paper Publication~~	+	==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~~: ~~Joshi, A~~.~~, Kosmopoulou, M~~.~~, Bayliss, R~~.	+	==About this Structure==
		+	[[4byi]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BYI OCA].

-	~~Description~~: ~~Aurora A~~ kinase ~~bound to a highly selective imidazopyridine inhibitor~~	+	==Reference==
		+	<ref group="xtra">PMID:024195668</ref><references group="xtra"/><references/>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Bayliss, R.]]
		+	[[Category: Joshi, A.]]
		+	[[Category: Kosmopoulou, M.]]
		+	[[Category: Cell cycle]]
		+	[[Category: Inhibitor]]
		+	[[Category: Transferase]]

OCA at 05:26, 10 October 2013

2013-10-10T05:26:03Z

←Older revision		Revision as of 05:26, 10 October 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4byi is ON HOLD	+	The entry 4byi is ON HOLD until Paper Publication

	Authors: Joshi, A., Kosmopoulou, M., Bayliss, R.		Authors: Joshi, A., Kosmopoulou, M., Bayliss, R.

	Description: Aurora A kinase bound to a highly selective imidazopyridine inhibitor		Description: Aurora A kinase bound to a highly selective imidazopyridine inhibitor

OCA at 07:13, 29 September 2013

2013-09-29T07:13:18Z

←Older revision		Revision as of 07:13, 29 September 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4byi is ON HOLD ~~until Paper Publication~~	+	The entry 4byi is ON HOLD

	Authors: Joshi, A., Kosmopoulou, M., Bayliss, R.		Authors: Joshi, A., Kosmopoulou, M., Bayliss, R.

	Description: Aurora A kinase bound to a highly selective imidazopyridine inhibitor		Description: Aurora A kinase bound to a highly selective imidazopyridine inhibitor