4a7c - Revision history

OCA at 11:21, 20 December 2023

2023-12-20T11:21:12Z

←Older revision		Revision as of 11:21, 20 December 2023
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	<StructureSection load='4a7c' size='340' side='right'caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4a7c' size='340' side='right'caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4a7c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A7C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A7C FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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]] 2.3Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bik\|2bik]], [[2xix\|2xix]], [[1ywv\|1ywv]], [[2bzj\|2bzj]], [[2c3i\|2c3i]], [[1yxu\|1yxu]], [[2j2i\|2j2i]], [[1yxt\|1yxt]], [[2bzh\|2bzh]], [[1yxs\|1yxs]], [[1xqz\|1xqz]], [[1yi3\|1yi3]], [[2xiz\|2xiz]], [[1yxv\|1yxv]], [[1xr1\|1xr1]], [[2xiy\|2xiy]], [[2bil\|2bil]], [[1yhs\|1yhs]], [[1yxx\|1yxx]], [[1xws\|1xws]], [[2xj1\|2xj1]], [[2bzk\|2bzk]], [[2xj0\|2xj0]], [[2xj2\|2xj2]], [[1yi4\|1yi4]], [[2bzi\|2bzi]]</div></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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [https://pdbe.org/4a7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [https://www.ebi.ac.uk/pdbsum/4a7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a7c 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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [https://pdbe.org/4a7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [https://www.ebi.ac.uk/pdbsum/4a7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a7c ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[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>	+	[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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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Mazzorana, M]]	+	[[Category: Mazzorana M]]
-	[[Category: Montoya, G]]	+	[[Category: Montoya G]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:49, 18 August 2022

2022-08-18T07:49:43Z

←Older revision		Revision as of 07:49, 18 August 2022
Line 3:		Line 3:
	<StructureSection load='4a7c' size='340' side='right'caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4a7c' size='340' side='right'caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4A7C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4a7c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A7C FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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='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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bik\|2bik]], [[2xix\|2xix]], [[1ywv\|1ywv]], [[2bzj\|2bzj]], [[2c3i\|2c3i]], [[1yxu\|1yxu]], [[2j2i\|2j2i]], [[1yxt\|1yxt]], [[2bzh\|2bzh]], [[1yxs\|1yxs]], [[1xqz\|1xqz]], [[1yi3\|1yi3]], [[2xiz\|2xiz]], [[1yxv\|1yxv]], [[1xr1\|1xr1]], [[2xiy\|2xiy]], [[2bil\|2bil]], [[1yhs\|1yhs]], [[1yxx\|1yxx]], [[1xws\|1xws]], [[2xj1\|2xj1]], [[2bzk\|2bzk]], [[2xj0\|2xj0]], [[2xj2\|2xj2]], [[1yi4\|1yi4]], [[2bzi\|2bzi]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bik\|2bik]], [[2xix\|2xix]], [[1ywv\|1ywv]], [[2bzj\|2bzj]], [[2c3i\|2c3i]], [[1yxu\|1yxu]], [[2j2i\|2j2i]], [[1yxt\|1yxt]], [[2bzh\|2bzh]], [[1yxs\|1yxs]], [[1xqz\|1xqz]], [[1yi3\|1yi3]], [[2xiz\|2xiz]], [[1yxv\|1yxv]], [[1xr1\|1xr1]], [[2xiy\|2xiy]], [[2bil\|2bil]], [[1yhs\|1yhs]], [[1yxx\|1yxx]], [[1xws\|1xws]], [[2xj1\|2xj1]], [[2bzk\|2bzk]], [[2xj0\|2xj0]], [[2xj2\|2xj2]], [[1yi4\|1yi4]], [[2bzi\|2bzi]]</div></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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [~~http~~://pdbe.org/4a7c PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4a7c PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4a7c 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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [https://pdbe.org/4a7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [https://www.ebi.ac.uk/pdbsum/4a7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a7c 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 22:

	==See Also==		==See Also==
-	*[[~~Proto-oncogene serine~~/threonine-protein kinase\|~~Proto-oncogene serine~~/threonine-protein kinase]]	+	*[[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/>
Line 28:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Mazzorana, M]]		[[Category: Mazzorana, M]]
	[[Category: Montoya, G]]		[[Category: Montoya, G]]

OCA at 09:33, 6 March 2019

2019-03-06T09:33:20Z

←Older revision		Revision as of 09:33, 6 March 2019
Line 1:		Line 1:

	==Crystal structure of PIM1 kinase with ETP46546==		==Crystal structure of PIM1 kinase with ETP46546==
-	<StructureSection load='4a7c' size='340' side='right' caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='4a7c' size='340' side='right'caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7C FirstGlance]. <br>		<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7C FirstGlance]. <br>

OCA at 13:04, 11 August 2016

2016-08-11T13:04:43Z

←Older revision		Revision as of 13:04, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of PIM1 kinase with ETP46546==		==Crystal structure of PIM1 kinase with ETP46546==
	<StructureSection load='4a7c' size='340' side='right' caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4a7c' size='340' side='right' caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>
Line 6:		Line 7:
	<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='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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bik\|2bik]], [[2xix\|2xix]], [[1ywv\|1ywv]], [[2bzj\|2bzj]], [[2c3i\|2c3i]], [[1yxu\|1yxu]], [[2j2i\|2j2i]], [[1yxt\|1yxt]], [[2bzh\|2bzh]], [[1yxs\|1yxs]], [[1xqz\|1xqz]], [[1yi3\|1yi3]], [[2xiz\|2xiz]], [[1yxv\|1yxv]], [[1xr1\|1xr1]], [[2xiy\|2xiy]], [[2bil\|2bil]], [[1yhs\|1yhs]], [[1yxx\|1yxx]], [[1xws\|1xws]], [[2xj1\|2xj1]], [[2bzk\|2bzk]], [[2xj0\|2xj0]], [[2xj2\|2xj2]], [[1yi4\|1yi4]], [[2bzi\|2bzi]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bik\|2bik]], [[2xix\|2xix]], [[1ywv\|1ywv]], [[2bzj\|2bzj]], [[2c3i\|2c3i]], [[1yxu\|1yxu]], [[2j2i\|2j2i]], [[1yxt\|1yxt]], [[2bzh\|2bzh]], [[1yxs\|1yxs]], [[1xqz\|1xqz]], [[1yi3\|1yi3]], [[2xiz\|2xiz]], [[1yxv\|1yxv]], [[1xr1\|1xr1]], [[2xiy\|2xiy]], [[2bil\|2bil]], [[1yhs\|1yhs]], [[1yxx\|1yxx]], [[1xws\|1xws]], [[2xj1\|2xj1]], [[2bzk\|2bzk]], [[2xj0\|2xj0]], [[2xj2\|2xj2]], [[1yi4\|1yi4]], [[2bzi\|2bzi]]</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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [http://www.ebi.ac.uk/pdbsum/4a7c 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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [http://pdbe.org/4a7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [http://www.ebi.ac.uk/pdbsum/4a7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a7c 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 4a7c" style="background-color:#fffaf0;"></div>

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

OCA at 07:59, 14 January 2015

2015-01-14T07:59:17Z

←Older revision		Revision as of 07:59, 14 January 2015
Line 2:		Line 2:
	<StructureSection load='4a7c' size='340' side='right' caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4a7c' size='340' side='right' caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7C FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
Line 25:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Mazzorana, M]]		[[Category: Mazzorana, M]]
	[[Category: Montoya, G]]		[[Category: Montoya, G]]

OCA at 02:02, 25 December 2014

2014-12-25T02:02:15Z

←Older revision		Revision as of 02:02, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7C FirstGlance]. <br>		<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7C FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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">[[2bik\|2bik]], [[2xix\|2xix]], [[1ywv\|1ywv]], [[2bzj\|2bzj]], [[2c3i\|2c3i]], [[1yxu\|1yxu]], [[2j2i\|2j2i]], [[1yxt\|1yxt]], [[2bzh\|2bzh]], [[1yxs\|1yxs]], [[1xqz\|1xqz]], [[1yi3\|1yi3]], [[2xiz\|2xiz]], [[1yxv\|1yxv]], [[1xr1\|1xr1]], [[2xiy\|2xiy]], [[2bil\|2bil]], [[1yhs\|1yhs]], [[1yxx\|1yxx]], [[1xws\|1xws]], [[2xj1\|2xj1]], [[2bzk\|2bzk]], [[2xj0\|2xj0]], [[2xj2\|2xj2]], [[1yi4\|1yi4]], [[2bzi\|2bzi]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bik\|2bik]], [[2xix\|2xix]], [[1ywv\|1ywv]], [[2bzj\|2bzj]], [[2c3i\|2c3i]], [[1yxu\|1yxu]], [[2j2i\|2j2i]], [[1yxt\|1yxt]], [[2bzh\|2bzh]], [[1yxs\|1yxs]], [[1xqz\|1xqz]], [[1yi3\|1yi3]], [[2xiz\|2xiz]], [[1yxv\|1yxv]], [[1xr1\|1xr1]], [[2xiy\|2xiy]], [[2bil\|2bil]], [[1yhs\|1yhs]], [[1yxx\|1yxx]], [[1xws\|1xws]], [[2xj1\|2xj1]], [[2bzk\|2bzk]], [[2xj0\|2xj0]], [[2xj2\|2xj2]], [[1yi4\|1yi4]], [[2bzi\|2bzi]]</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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [http://www.ebi.ac.uk/pdbsum/4a7c 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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [http://www.ebi.ac.uk/pdbsum/4a7c 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:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Mazzorana, M.]]	+	[[Category: Mazzorana, M]]
-	[[Category: Montoya, G.]]	+	[[Category: Montoya, G]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Protein kinase]]		[[Category: Protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 08:22, 5 June 2014

2014-06-05T08:22:47Z

←Older revision		Revision as of 08:22, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~4a7c.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of PIM1 kinase with ETP46546==
		+	<StructureSection load='4a7c' size='340' side='right' caption='[[4a7c]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7C FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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">[[2bik\|2bik]], [[2xix\|2xix]], [[1ywv\|1ywv]], [[2bzj\|2bzj]], [[2c3i\|2c3i]], [[1yxu\|1yxu]], [[2j2i\|2j2i]], [[1yxt\|1yxt]], [[2bzh\|2bzh]], [[1yxs\|1yxs]], [[1xqz\|1xqz]], [[1yi3\|1yi3]], [[2xiz\|2xiz]], [[1yxv\|1yxv]], [[1xr1\|1xr1]], [[2xiy\|2xiy]], [[2bil\|2bil]], [[1yhs\|1yhs]], [[1yxx\|1yxx]], [[1xws\|1xws]], [[2xj1\|2xj1]], [[2bzk\|2bzk]], [[2xj0\|2xj0]], [[2xj2\|2xj2]], [[1yi4\|1yi4]], [[2bzi\|2bzi]]</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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [http://www.ebi.ac.uk/pdbsum/4a7c PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	PIM kinases have become targets of interest due to their association with biochemical mechanisms affecting survival, proliferation and cytokine production. 1,2,3-Triazolo[4,5-b]pyridines were identified as PIM inhibitors applying a scaffold hopping approach. Initial exploration around this scaffold and X-ray crystallographic data are hereby described.

-	<!--	+	Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors.,Pastor J, Oyarzabal J, Saluste G, Alvarez RM, Rivero V, Ramos F, Cendon E, Blanco-Aparicio C, Ajenjo N, Cebria A, Albarran MI, Cebrian D, Corrionero A, Fominaya J, Montoya G, Mazzorana M Bioorg Med Chem Lett. 2012 Feb 15;22(4):1591-7. Epub 2012 Jan 5. PMID:22266039<ref>PMID:22266039</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_4a7c"~~, ~~creates the "Structure Box" on the page~~.	+
-	~~You may change the PDB parameter~~ (~~which sets the PDB file loaded into the applet~~)	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~	+
-	~~or leave the SCENE parameter empty for the default display.~~	+
-	-->	+
-	~~{{STRUCTURE_4a7c\| PDB=4a7c \| SCENE= }}~~	+

-	~~===Crystal structure~~ of ~~PIM1 kinase with ETP46546===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	~~<!--~~	+	*[[Proto-oncogene serine/threonine-protein kinase\|Proto-oncogene serine/threonine-protein kinase]]
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22266039}}, adds the Publication Abstract to the page~~	+	== References ==
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 22266039 is the PubMed ID number.~~	+	<references/>
-	~~-->~~	+	__TOC__
-	~~{{ABSTRACT_PUBMED_22266039}}~~	+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[~~4a7c]] 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=4A7C OCA~~].	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022266039<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mazzorana, M.]]		[[Category: Mazzorana, M.]]

OCA at 04:59, 23 May 2012

2012-05-23T04:59:58Z

←Older revision		Revision as of 04:59, 23 May 2012
Line 1:		Line 1:
-	[[Image:4a7c.~~jpg~~\|left\|200px]]	+	[[Image:4a7c.png\|left\|200px]]

	<!--		<!--

OCA at 06:39, 15 February 2012

2012-02-15T06:39:08Z

←Older revision		Revision as of 06:39, 15 February 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4a7c.jpg\|left\|200px]]

-	The ~~entry 4a7c~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_4a7c", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_4a7c\| PDB=4a7c \| SCENE= }}

-	~~Authors: Mazzorana, M., Montoya, G.~~	+	===Crystal structure of PIM1 kinase with ETP46546===

-	~~Description~~: ~~Crystal~~ structure ~~of PIM1 kinase~~ with ~~ETP46546~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22266039}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22266039 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22266039}}
		+
		+	==About this Structure==
		+	[[4a7c]] 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=4A7C OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022266039</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Mazzorana, M.]]
		+	[[Category: Montoya, G.]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase]]

OCA: Protected "4a7c" [edit=sysop:move=sysop]

2011-11-23T18:45:44Z

Protected "4a7c" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:45, 23 November 2011