4ty1 - Revision history

OCA at 00:48, 28 December 2023

2023-12-28T00:48:38Z

←Older revision		Revision as of 00:48, 28 December 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ty1]] 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=4TY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TY1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ty1]] 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=4TY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TY1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [https://pdbe.org/4ty1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [https://www.ebi.ac.uk/pdbsum/4ty1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ty1 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=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [https://pdbe.org/4ty1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [https://www.ebi.ac.uk/pdbsum/4ty1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ty1 ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 4ty1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ty1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:51, 22 March 2023

2023-03-22T07:51:37Z

←Older revision		Revision as of 07:51, 22 March 2023
Line 1:		Line 1:

	==Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor.==		==Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor.==
-	<StructureSection load='4ty1' size='340' side='right' caption='[[4ty1]], [[Resolution\|resolution]] 2.70Å' scene=''>	+	<StructureSection load='4ty1' size='340' side='right'caption='[[4ty1]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ty1]] 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=4TY1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4TY1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ty1]] 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=4TY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TY1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [https://pdbe.org/4ty1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [https://www.ebi.ac.uk/pdbsum/4ty1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ty1 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=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [~~http~~://pdbe.org/4ty1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ty1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ty1 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>	+	[https://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4ty1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ty1" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Mohr, C]]	+	[[Category: Mohr C]]
-	~~[[Category: Serine/threonine-protein kinase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 09:18, 22 November 2017

2017-11-22T09:18:38Z

←Older revision		Revision as of 09:18, 22 November 2017
Line 3:		Line 3:
	<StructureSection load='4ty1' size='340' side='right' caption='[[4ty1]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4ty1' size='340' side='right' caption='[[4ty1]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ty1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TY1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TY1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ty1]] 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=4TY1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TY1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([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=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [http://pdbe.org/4ty1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ty1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ty1 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [http://pdbe.org/4ty1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ty1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ty1 ProSAT]</span></td></tr>
Line 26:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Mohr, C]]		[[Category: Mohr, C]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 01:09, 19 January 2017

2017-01-19T01:09:49Z

←Older revision		Revision as of 01:09, 19 January 2017
Line 1:		Line 1:
		+
	==Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor.==		==Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor.==
	<StructureSection load='4ty1' size='340' side='right' caption='[[4ty1]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4ty1' size='340' side='right' caption='[[4ty1]], [[Resolution\|resolution]] 2.70Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='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=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ty1 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=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [http://pdbe.org/4ty1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ty1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ty1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4ty1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:45, 7 February 2015

2015-02-07T15:45:12Z

←Older revision		Revision as of 15:45, 7 February 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor.==
		+	<StructureSection load='4ty1' size='340' side='right' caption='[[4ty1]], [[Resolution\|resolution]] 2.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ty1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TY1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TY1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38W:N-TERT-BUTYL-5-[3-(4-CYCLOPROPYLPYRIMIDIN-2-YL)-1H-INDOL-5-YL]-1,3,4-OXADIAZOL-2-AMINE'>38W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ty1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ty1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ty1 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers. These findings suggest that inhibition of Pim signaling by a small molecule Pim-1,2 inhibitor could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal starting from the highly Pim-selective indole-thiadiazole compound (1), which was derived from a nonselective hit identified in a high throughput screening campaign. Optimization of this compound's potency and its pharmacokinetic properties resulted in the discovery of compound 29. Cyclopropane 29 was found to exhibit excellent enzymatic potency on the Pim-1 and Pim-2 isoforms (Ki values of 0.55nM and 0.28nM, respectively), and found to inhibit the phosphorylation of BAD in the Pim-overexpressing KMS-12 cell line (IC50=150nM). This compound had moderate clearance and bioavailability in rat (CL=2.42L/kg/h; %F=24) and exhibited a dose-dependent inhibition of p-BAD in KMS-12 tumor pharmacodynamic (PD) model with an EC50 value of 6.74muM (18mug/mL) when dosed at 10, 30, 100 and 200mg/kg po in mice.

-	The ~~entry 4ty1 is ON HOLD until Paper Publication~~	+	The discovery and optimization of aminooxadiazoles as potent Pim kinase inhibitors.,Wurz RP, Pettus LH, Jackson C, Wu B, Wang HL, Herberich B, Cee V, Lanman BA, Reed AB, Chavez F Jr, Nixey T, Laszlo J 3rd, Wang P, Nguyen Y, Sastri C, Guerrero N, Winston J, Lipford JR, Lee MR, Andrews KL, Mohr C, Xu Y, Zhou Y, Reid DL, Tasker AS Bioorg Med Chem Lett. 2015 Feb 15;25(4):847-55. doi: 10.1016/j.bmcl.2014.12.067. , Epub 2015 Jan 7. PMID:25599837<ref>PMID:25599837</ref>

-	~~Authors: Mohr~~, C.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Crystal structure~~ of ~~human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor~~.	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Mohr, C]]		[[Category: Mohr, C]]
		+	[[Category: Serine/threonine-protein kinase]]
		+	[[Category: Transferase]]

OCA at 17:58, 24 December 2014

2014-12-24T17:58:22Z

←Older revision		Revision as of 17:58, 24 December 2014
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	Description: Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor.		Description: Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor.
		+	[[Category: Unreleased Structures]]
		+	[[Category: Mohr, C]]

OCA: Protected "4ty1" [edit=sysop:move=sysop]

2014-07-16T09:56:57Z

Protected "4ty1" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:56, 16 July 2014

OCA: New page: '''Unreleased structure''' The entry 4ty1 is ON HOLD until Paper Publication Authors: Mohr, C. Description: Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-i...

2014-07-16T09:56:57Z

New page: '''Unreleased structure''' The entry 4ty1 is ON HOLD until Paper Publication Authors: Mohr, C. Description: Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-i...

New page

'''Unreleased structure'''

The entry 4ty1 is ON HOLD until Paper Publication

Authors: Mohr, C.

Description: Crystal structure of human Pim-1 kinase in complex with an aminooxadiazole-indole inhibitor.