3f2a - Revision history

OCA at 05:48, 17 October 2024

2024-10-17T05:48:28Z

← Older revision		Revision as of 05:48, 17 October 2024
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	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f2/3f2a_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f2/3f2a_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/~~initialview01~~.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>

OCA at 00:28, 28 December 2023

2023-12-28T00:28:05Z

← Older revision		Revision as of 00:28, 28 December 2023
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	<StructureSection load='3f2a' size='340' side='right'caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3f2a' size='340' side='right'caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3f2a]] 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=3F2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F2A FirstGlance]. <br>		<table><tr><td colspan='2'>[[3f2a]] 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=3F2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F2A FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=985:(2E)-3-{3-[6-(4-METHYL-1,4-DIAZEPAN-1-YL)PYRAZIN-2-YL]PHENYL}PROP-2-ENOIC+ACID'>985</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.9Å</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=985:(2E)-3-{3-[6-(4-METHYL-1,4-DIAZEPAN-1-YL)PYRAZIN-2-YL]PHENYL}PROP-2-ENOIC+ACID'>985</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([https://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'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [https://pdbe.org/3f2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [https://www.ebi.ac.uk/pdbsum/3f2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f2a 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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [https://pdbe.org/3f2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [https://www.ebi.ac.uk/pdbsum/3f2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f2a 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific serine/threonine protein kinase]]~~		[[Category: Qian K]]
	[[Category: Qian, K]]
	~~[[Category: Alternative initiation]]~~
	~~[[Category: Atp-binding]]~~
	~~[[Category: Cell membrane]]~~
	~~[[Category: Cytoplasm]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Manganese]]~~
	~~[[Category: Membrane]]~~
	~~[[Category: Metal-binding]]~~
	~~[[Category: Nucleotide-binding]]~~
	~~[[Category: Nucleus]]~~
	~~[[Category: Phosphoprotein]]~~
	~~[[Category: Polymorphism]]~~
	~~[[Category: Potein kinase fold]]~~
	~~[[Category: Proto-oncogene]]~~
	~~[[Category: Serine/threonine-protein kinase]]~~
	~~[[Category: Transferase~~]]

OCA at 09:21, 23 February 2022

2022-02-23T09:21:59Z

← Older revision		Revision as of 09:21, 23 February 2022
Line 1:		Line 1:

	==Crystal structure of human Pim-1 in complex with DAPPA==		==Crystal structure of human Pim-1 in complex with DAPPA==
	<StructureSection load='3f2a' size='340' side='right' caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3f2a' size='340' side='right'caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3f2a]] 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=3F2A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3F2A FirstGlance]. <br>		<table><tr><td colspan='2'>[[3f2a]] 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=3F2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F2A FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=985:(2E)-3-{3-[6-(4-METHYL-1,4-DIAZEPAN-1-YL)PYRAZIN-2-YL]PHENYL}PROP-2-ENOIC+ACID'>985</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=985:(2E)-3-{3-[6-(4-METHYL-1,4-DIAZEPAN-1-YL)PYRAZIN-2-YL]PHENYL}PROP-2-ENOIC+ACID'>985</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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='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 ([https://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'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [~~http~~://pdbe.org/3f2a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3f2a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3f2a 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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [https://pdbe.org/3f2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [https://www.ebi.ac.uk/pdbsum/3f2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f2a 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==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 39:		Line 40:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Qian, K]]		[[Category: Qian, K]]

OCA at 22:01, 2 December 2018

2018-12-02T22:01:32Z

← Older revision		Revision as of 22:01, 2 December 2018
Line 1:		Line 1:

	==Crystal structure of human Pim-1 in complex with DAPPA==		==Crystal structure of human Pim-1 in complex with DAPPA==
	<StructureSection load='3f2a' size='340' side='right' caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3f2a' size='340' side='right' caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>
Line 7:		Line 8:
	<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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [http://pdbe.org/3f2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [http://www.ebi.ac.uk/pdbsum/3f2a 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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [http://pdbe.org/3f2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [http://www.ebi.ac.uk/pdbsum/3f2a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f2a ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f2/3f2a_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f2/3f2a_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 43:		Line 44:
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Cell membrane]]		[[Category: Cell membrane]]
			[[Category: Cytoplasm]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Manganese]]		[[Category: Manganese]]
Line 50:		Line 52:
	[[Category: Nucleus]]		[[Category: Nucleus]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
			[[Category: Polymorphism]]
	[[Category: Potein kinase fold]]		[[Category: Potein kinase fold]]
	[[Category: Proto-oncogene]]		[[Category: Proto-oncogene]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 19:24, 7 February 2016

2016-02-07T19:24:18Z

← Older revision		Revision as of 19:24, 7 February 2016
Line 2:		Line 2:
	<StructureSection load='3f2a' size='340' side='right' caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3f2a' size='340' side='right' caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3f2a]] 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=3F2A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F2A FirstGlance]. <br>		<table><tr><td colspan='2'>[[3f2a]] 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=3F2A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F2A FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=985:(2E)-3-{3-[6-(4-METHYL-1,4-DIAZEPAN-1-YL)PYRAZIN-2-YL]PHENYL}PROP-2-ENOIC+ACID'>985</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=985:(2E)-3-{3-[6-(4-METHYL-1,4-DIAZEPAN-1-YL)PYRAZIN-2-YL]PHENYL}PROP-2-ENOIC+ACID'>985</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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='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 ~~Homo sapiens~~])</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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [http://www.ebi.ac.uk/pdbsum/3f2a 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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [http://pdbe.org/3f2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [http://www.ebi.ac.uk/pdbsum/3f2a PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3f2a ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	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 3f2a" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Qian, K]]		[[Category: Qian, K]]

OCA at 17:42, 24 December 2014

2014-12-24T17:42:21Z

← Older revision		Revision as of 17:42, 24 December 2014
Line 9:		Line 9:
	<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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [http://www.ebi.ac.uk/pdbsum/3f2a 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=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [http://www.ebi.ac.uk/pdbsum/3f2a 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 08:45, 26 November 2014

2014-11-26T08:45:40Z

← Older revision		Revision as of 08:45, 26 November 2014
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	[[Image:~~3f2a~~.~~png~~\|~~left~~\|~~200px~~]]		==Crystal structure of human Pim-1 in complex with DAPPA==
			<StructureSection load='3f2a' size='340' side='right' caption='[[3f2a]], [[Resolution\|resolution]] 1.90Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[3f2a]] 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=3F2A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F2A FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=985:(2E)-3-{3-[6-(4-METHYL-1,4-DIAZEPAN-1-YL)PYRAZIN-2-YL]PHENYL}PROP-2-ENOIC+ACID'>985</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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='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 Homo sapiens])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3f2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f2a RCSB], [http://www.ebi.ac.uk/pdbsum/3f2a PDBsum]</span></td></tr>
			</table>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f2/3f2a_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed.

	~~{{STRUCTURE_3f2a\| PDB=3f2a \| SCENE= }}~~		Hit to Lead Account of the Discovery of a New Class of Inhibitors of Pim Kinases and Crystallographic Studies Revealing an Unusual Kinase Binding Mode (dagger).,Qian K, Wang L, Cywin CL, Farmer BT, Hickey E, Homon C, Jakes S, Kashem MA, Lee G, Leonard S, Li J, Magboo R, Mao W, Pack E, Peng C, Prokopowicz A, Welzel M, Wolak J, Morwick T J Med Chem. 2009 Mar 3. PMID:19256503<ref>PMID:19256503</ref>

	~~===Crystal structure~~ of ~~human Pim-1 in complex with DAPPA===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_19256503}}~~		==See Also==
			*[[Proto-oncogene serine/threonine-protein kinase\|Proto-oncogene serine/threonine-protein kinase]]
	==~~About this Structure~~==		== References ==
	[[~~3f2a]] 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=3F2A OCA~~].		<references/>
			__TOC__
	==~~Reference~~==		</StructureSection>
	<~~ref group="xtra">PMID:019256503<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Qian, K.]]		[[Category: Qian, K]]
	[[Category: Alternative initiation]]		[[Category: Alternative initiation]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]

OCA: Protected "3f2a" [edit=sysop:move=sysop]

2013-02-13T11:06:44Z

Protected "3f2a" [edit=sysop:move=sysop]

← Older revision	Revision as of 11:06, 13 February 2013
(No difference)

OCA at 11:06, 13 February 2013

2013-02-13T11:06:41Z

← Older revision		Revision as of 11:06, 13 February 2013
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	~~{{Seed}}~~
	[[Image:3f2a.png\|left\|200px]]		[[Image:3f2a.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3f2a", 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_3f2a\| PDB=3f2a \| SCENE= }}		{{STRUCTURE_3f2a\| PDB=3f2a \| SCENE= }}

	===Crystal structure of human Pim-1 in complex with DAPPA===		===Crystal structure of human Pim-1 in complex with DAPPA===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_19256503}}, adds the Publication Abstract to the page~~
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	{{ABSTRACT_PUBMED_19256503}}		{{ABSTRACT_PUBMED_19256503}}

	==About this Structure==		==About this Structure==
	~~3F2A~~ is a 1 chain structure of 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=3F2A OCA].		[[3f2a]] 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=3F2A OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~19256503~~</ref><references group="xtra"/>		<ref group="xtra">PMID:019256503</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
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	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Cell membrane]]		[[Category: Cell membrane]]
	~~[[Category: Cytoplasm]]~~
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Manganese]]		[[Category: Manganese]]
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	[[Category: Nucleus]]		[[Category: Nucleus]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	~~[[Category: Polymorphism]]~~
	[[Category: Potein kinase fold]]		[[Category: Potein kinase fold]]
	[[Category: Proto-oncogene]]		[[Category: Proto-oncogene]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 22 10:58:07 2009''~~

OCA at 07:58, 22 April 2009

2009-04-22T07:58:08Z

← Older revision		Revision as of 07:58, 22 April 2009
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	{{Seed}}		{{Seed}}
	[[Image:3f2a.~~jpg~~\|left\|200px]]		[[Image:3f2a.png\|left\|200px]]

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	[[Category: Transferase]]		[[Category: Transferase]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Mar 11 11~~:25:54 2009''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 22 10:58:07 2009''