4n70 - Revision history

OCA at 08:13, 11 January 2023

OCA — Wed, 11 Jan 2023 08:13:00 GMT

←Older revision		Revision as of 08:13, 11 January 2023
Line 1:		Line 1:

	==Pim1 Complexed with a pyridylcarboxamide==		==Pim1 Complexed with a pyridylcarboxamide==
-	<StructureSection load='4n70' size='340' side='right' caption='[[4n70]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='4n70' size='340' side='right'caption='[[4n70]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4n70]] 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=4N70 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4N70 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4n70]] 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=4N70 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N70 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HX:N-{4-[(3R,4R,5S)-3-AMINO-4-HYDROXY-5-METHYLPIPERIDIN-1-YL]PYRIDIN-3-YL}-6-(2,6-DIFLUOROPHENYL)-5-FLUOROPYRIDINE-2-CARBOXAMIDE'>2HX</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2HX:N-{4-[(3R,4R,5S)-3-AMINO-4-HYDROXY-5-METHYLPIPERIDIN-1-YL]PYRIDIN-3-YL}-6-(2,6-DIFLUOROPHENYL)-5-FLUOROPYRIDINE-2-CARBOXAMIDE'>2HX</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=4n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n70 OCA], [https://pdbe.org/4n70 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n70 RCSB], [https://www.ebi.ac.uk/pdbsum/4n70 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n70 ProSAT]</span></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n6y\|4n6y]], [[4n6z\|4n6z]]</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='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=4n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n70 OCA], [~~http~~://pdbe.org/4n70 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4n70 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4n70 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4n70 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 ==
Line 22:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4n70" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4n70" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
		+	*[[3D structures of pim-1\|3D structures of pim-1]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Bellamacina~~, C R~~]]	+	[[Category: Bellamacina CR]]
-	[[Category: Burger~~, M T~~]]	+	[[Category: Burger MT]]
-	[[Category: Bussiere, D]]	+	[[Category: Bussiere D]]
-	[[Category: Le, V]]	+	[[Category: Le V]]
-	[[Category: Shu, W]]	+	[[Category: Shu W]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 20:20, 4 August 2016

OCA — Thu, 04 Aug 2016 20:20:28 GMT

←Older revision		Revision as of 20:20, 4 August 2016
Line 1:		Line 1:
		+
	==Pim1 Complexed with a pyridylcarboxamide==		==Pim1 Complexed with a pyridylcarboxamide==
	<StructureSection load='4n70' size='340' side='right' caption='[[4n70]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='4n70' size='340' side='right' caption='[[4n70]], [[Resolution\|resolution]] 2.10Å' scene=''>
Line 8:		Line 9:
	<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='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=4n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n70 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n70 RCSB], [http://www.ebi.ac.uk/pdbsum/4n70 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=4n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n70 OCA], [http://pdbe.org/4n70 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n70 RCSB], [http://www.ebi.ac.uk/pdbsum/4n70 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n70 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	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 4n70" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:16, 24 December 2014

OCA — Wed, 24 Dec 2014 19:16:11 GMT

←Older revision		Revision as of 19:16, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4n70]] 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=4N70 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N70 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4n70]] 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=4N70 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N70 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HX:N-{4-[(3R,4R,5S)-3-AMINO-4-HYDROXY-5-METHYLPIPERIDIN-1-YL]PYRIDIN-3-YL}-6-(2,6-DIFLUOROPHENYL)-5-FLUOROPYRIDINE-2-CARBOXAMIDE'>2HX</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HX:N-{4-[(3R,4R,5S)-3-AMINO-4-HYDROXY-5-METHYLPIPERIDIN-1-YL]PYRIDIN-3-YL}-6-(2,6-DIFLUOROPHENYL)-5-FLUOROPYRIDINE-2-CARBOXAMIDE'>2HX</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n6y\|4n6y]], [[4n6z\|4n6z]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n6y\|4n6y]], [[4n6z\|4n6z]]</td></tr>
-	<tr><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='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><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n70 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n70 RCSB], [http://www.ebi.ac.uk/pdbsum/4n70 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=4n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n70 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n70 RCSB], [http://www.ebi.ac.uk/pdbsum/4n70 PDBsum]</span></td></tr>
-	<table>	+	</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 26:
	[[Category: Human]]		[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Bellamacina, C R.]]	+	[[Category: Bellamacina, C R]]
-	[[Category: Burger, M T.]]	+	[[Category: Burger, M T]]
-	[[Category: Bussiere, D.]]	+	[[Category: Bussiere, D]]
-	[[Category: Le, V.]]	+	[[Category: Le, V]]
-	[[Category: Shu, W.]]	+	[[Category: Shu, W]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Phosphorylation]]		[[Category: Phosphorylation]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:15, 2 July 2014

OCA — Wed, 02 Jul 2014 06:15:37 GMT

←Older revision		Revision as of 06:15, 2 July 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4n70~~\| ~~PDB~~=4n70 \| ~~SCENE~~= }}	+	==Pim1 Complexed with a pyridylcarboxamide==
-	===~~Pim1 Complexed~~ with ~~a pyridylcarboxamide~~===	+	<StructureSection load='4n70' size='340' side='right' caption='[[4n70]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4n70]] 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=4N70 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N70 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HX:N-{4-[(3R,4R,5S)-3-AMINO-4-HYDROXY-5-METHYLPIPERIDIN-1-YL]PYRIDIN-3-YL}-6-(2,6-DIFLUOROPHENYL)-5-FLUOROPYRIDINE-2-CARBOXAMIDE'>2HX</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n6y\|4n6y]], [[4n6z\|4n6z]]</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n70 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n70 RCSB], [http://www.ebi.ac.uk/pdbsum/4n70 PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Proviral insertion of Moloney virus (PIM) 1, 2, and 3 kinases are serine/threonine kinases that normally function in survival and proliferation of hematopoietic cells. As high expression of PIM1, 2, and 3 is frequently observed in many human malignancies, including multiple myeloma, non-Hodgkins lymphoma, and myeloid leukemias, there is interest in determining whether selective PIM inhibition can improve outcomes of these human cancers. Herein, we describe our efforts toward this goal. The structure guided optimization of a singleton high throughput screening hit in which the potency against all three PIM isoforms was increased >10,000-fold to yield compounds with pan PIM K is < 10 pM, nanomolar cellular potency, and in vivo activity in an acute myeloid leukemia Pim-dependent tumor model is described.

-	~~==Function==~~	+	Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM Kinase Inhibitors.,Burger MT, Han W, Lan J, Nishiguchi G, Bellamacina C, Lindval M, Atallah G, Ding Y, Mathur M, McBride C, Beans EL, Muller K, Tamez V, Zhang Y, Huh K, Feucht P, Zavorotinskaya T, Dai Y, Holash J, Castillo J, Langowski J, Wang Y, Chen MY, Garcia PD ACS Med Chem Lett. 2013 Oct 15;4(12):1193-7. doi: 10.1021/ml400307j. eCollection , 2013 Dec 12. PMID:24900629<ref>PMID:24900629</ref>
-	~~[[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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4n70]] 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=4N70 OCA].~~	+	</div>
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
-	[[Category: ~~Homo sapiens~~]]	+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bellamacina, C R.]]		[[Category: Bellamacina, C R.]]

OCA at 07:55, 6 November 2013

OCA — Wed, 06 Nov 2013 07:55:32 GMT

←Older revision		Revision as of 07:55, 6 November 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4n70\| PDB=4n70 \| SCENE= }}
		+	===Pim1 Complexed with a pyridylcarboxamide===

-	The ~~entry 4n70 is ON HOLD~~	+	==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>

-	~~Authors~~: ~~Bellamacina, C~~.R.~~, Le, V~~.~~, Shu, W~~.~~, Burger, M~~.T.~~, Bussiere, D~~.	+	==About this Structure==
		+	[[4n70]] 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=4N70 OCA].

-	~~Description~~: ~~Pim1 Complexed with a pyridylcarboxamide~~	+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Bellamacina, C R.]]
		+	[[Category: Burger, M T.]]
		+	[[Category: Bussiere, D.]]
		+	[[Category: Le, V.]]
		+	[[Category: Shu, W.]]
		+	[[Category: Kinase]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:02, 6 November 2013

OCA — Wed, 06 Nov 2013 07:02:56 GMT

←Older revision		Revision as of 07:02, 6 November 2013
Line 3:		Line 3:
	The entry 4n70 is ON HOLD		The entry 4n70 is ON HOLD

-	Authors: Bellamacina, C.R., Le, V., Shu, W., Burger, M. T., Bussiere, D.	+	Authors: Bellamacina, C.R., Le, V., Shu, W., Burger, M.T., Bussiere, D.

	Description: Pim1 Complexed with a pyridylcarboxamide		Description: Pim1 Complexed with a pyridylcarboxamide

OCA: Protected "4n70" [edit=sysop:move=sysop]

OCA — Wed, 23 Oct 2013 06:16:34 GMT

Protected "4n70" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:16, 23 October 2013

OCA: New page: '''Unreleased structure''' The entry 4n70 is ON HOLD Authors: Bellamacina, C.R., Le, V., Shu, W., Burger, M. T., Bussiere, D. Description: Pim1 Complexed with a pyridylcarboxamide

OCA — Wed, 23 Oct 2013 06:16:33 GMT

New page: '''Unreleased structure''' The entry 4n70 is ON HOLD Authors: Bellamacina, C.R., Le, V., Shu, W., Burger, M. T., Bussiere, D. Description: Pim1 Complexed with a pyridylcarboxamide

New page

'''Unreleased structure'''

The entry 4n70 is ON HOLD

Authors: Bellamacina, C.R., Le, V., Shu, W., Burger, M. T., Bussiere, D.

Description: Pim1 Complexed with a pyridylcarboxamide