4as0 - Revision history

OCA at 11:34, 20 December 2023

OCA — Wed, 20 Dec 2023 11:34:23 GMT

←Older revision		Revision as of 11:34, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='4as0' size='340' side='right'caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4as0' size='340' side='right'caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=RPS:PHTALIMIDE~~-~~RUTHENIUM+COMPLEX'>RPS</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='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xqz\|1xqz]], [[1xr1\|1xr1]], [[1xws\|1xws]], [[1yhs\|1yhs]], [[1yi3\|1yi3]], [[1yi4\|1yi4]], [[1ywv\|1ywv]], [[1yxs\|1yxs]], [[1yxt\|1yxt]], [[1yxu\|1yxu]], [[1yxv\|1yxv]], [[1yxx\|1yxx]], [[2bik\|2bik]], [[2bil\|2bil]], [[2bzh\|2bzh]], [[2bzi\|2bzi]], [[2bzj\|2bzj]], [[2bzk\|2bzk]], [[2c3i\|2c3i]], [[2j2i\|2j2i]], [[2xix\|2xix]], [[2xiy\|2xiy]], [[2xiz\|2xiz]], [[2xj0\|2xj0]], [[2xj1\|2xj1]], [[2xj2\|2xj2]], [[4a7c\|4a7c]], [[4alu\|4alu]], [[4alv\|4alv]], [[4alw\|4alw]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RPS:PHTALIMIDE-RUTHENIUM+COMPLEX'>RPS</scene></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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [https://pdbe.org/4as0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [https://www.ebi.ac.uk/pdbsum/4as0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4as0 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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [https://pdbe.org/4as0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [https://www.ebi.ac.uk/pdbsum/4as0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4as0 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: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Blanck S]]
-	[[Category: Blanck, S]]	+	[[Category: Essen L-O]]
-	[[Category: Essen, L O]]	+	[[Category: Geisselbrecht Y]]
-	[[Category: Geisselbrecht, Y]]	+	[[Category: Harms K]]
-	[[Category: Harms, K]]	+	[[Category: Meggers E]]
-	[[Category: Meggers, E]]	+	[[Category: Middel S]]
-	[[Category: Middel, S]]	+	[[Category: Mietke T]]
-	[[Category: Mietke, T]]	+
-	~~[[Category: Kinase inhibitor]]~~	+
-	~~[[Category: Octasporine]]~~	+
-	~~[[Category: Pim1]]~~	+
-	~~[[Category: Ruthenium]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 05:44, 25 August 2022

OCA — Thu, 25 Aug 2022 05:44:24 GMT

←Older revision		Revision as of 05:44, 25 August 2022
Line 3:		Line 3:
	<StructureSection load='4as0' size='340' side='right'caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4as0' size='340' side='right'caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RPS:PHTALIMIDE-RUTHENIUM+COMPLEX'>RPS</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RPS:PHTALIMIDE-RUTHENIUM+COMPLEX'>RPS</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xqz\|1xqz]], [[1xr1\|1xr1]], [[1xws\|1xws]], [[1yhs\|1yhs]], [[1yi3\|1yi3]], [[1yi4\|1yi4]], [[1ywv\|1ywv]], [[1yxs\|1yxs]], [[1yxt\|1yxt]], [[1yxu\|1yxu]], [[1yxv\|1yxv]], [[1yxx\|1yxx]], [[2bik\|2bik]], [[2bil\|2bil]], [[2bzh\|2bzh]], [[2bzi\|2bzi]], [[2bzj\|2bzj]], [[2bzk\|2bzk]], [[2c3i\|2c3i]], [[2j2i\|2j2i]], [[2xix\|2xix]], [[2xiy\|2xiy]], [[2xiz\|2xiz]], [[2xj0\|2xj0]], [[2xj1\|2xj1]], [[2xj2\|2xj2]], [[4a7c\|4a7c]], [[4alu\|4alu]], [[4alv\|4alv]], [[4alw\|4alw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xqz\|1xqz]], [[1xr1\|1xr1]], [[1xws\|1xws]], [[1yhs\|1yhs]], [[1yi3\|1yi3]], [[1yi4\|1yi4]], [[1ywv\|1ywv]], [[1yxs\|1yxs]], [[1yxt\|1yxt]], [[1yxu\|1yxu]], [[1yxv\|1yxv]], [[1yxx\|1yxx]], [[2bik\|2bik]], [[2bil\|2bil]], [[2bzh\|2bzh]], [[2bzi\|2bzi]], [[2bzj\|2bzj]], [[2bzk\|2bzk]], [[2c3i\|2c3i]], [[2j2i\|2j2i]], [[2xix\|2xix]], [[2xiy\|2xiy]], [[2xiz\|2xiz]], [[2xj0\|2xj0]], [[2xj1\|2xj1]], [[2xj2\|2xj2]], [[4a7c\|4a7c]], [[4alu\|4alu]], [[4alv\|4alv]], [[4alw\|4alw]]</div></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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [~~http~~://pdbe.org/4as0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4as0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4as0 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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [https://pdbe.org/4as0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [https://www.ebi.ac.uk/pdbsum/4as0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4as0 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: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Blanck, S]]		[[Category: Blanck, S]]

OCA at 09:44, 6 March 2019

OCA — Wed, 06 Mar 2019 09:44:52 GMT

←Older revision		Revision as of 09:44, 6 March 2019
Line 1:		Line 1:

	==Cyclometalated Phthalimides as Protein Kinase Inhibitors==		==Cyclometalated Phthalimides as Protein Kinase Inhibitors==
-	<StructureSection load='4as0' size='340' side='right' caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='4as0' size='340' side='right'caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>

OCA at 23:34, 5 August 2016

OCA — Fri, 05 Aug 2016 23:34:37 GMT

←Older revision		Revision as of 23:34, 5 August 2016
Line 1:		Line 1:
		+
	==Cyclometalated Phthalimides as Protein Kinase Inhibitors==		==Cyclometalated Phthalimides as Protein Kinase Inhibitors==
	<StructureSection load='4as0' size='340' side='right' caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4as0' size='340' side='right' caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RPS:PHTALIMIDE-RUTHENIUM+COMPLEX'>RPS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RPS:PHTALIMIDE-RUTHENIUM+COMPLEX'>RPS</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xqz\|1xqz]], [[1xr1\|1xr1]], [[1xws\|1xws]], [[1yhs\|1yhs]], [[1yi3\|1yi3]], [[1yi4\|1yi4]], [[1ywv\|1ywv]], [[1yxs\|1yxs]], [[1yxt\|1yxt]], [[1yxu\|1yxu]], [[1yxv\|1yxv]], [[1yxx\|1yxx]], [[2bik\|2bik]], [[2bil\|2bil]], [[2bzh\|2bzh]], [[2bzi\|2bzi]], [[2bzj\|2bzj]], [[2bzk\|2bzk]], [[2c3i\|2c3i]], [[2j2i\|2j2i]], [[2xix\|2xix]], [[2xiy\|2xiy]], [[2xiz\|2xiz]], [[2xj0\|2xj0]], [[2xj1\|2xj1]], [[2xj2\|2xj2]], [[4a7c\|4a7c]], [[4alu\|4alu]], [[4alv\|4alv]], [[4alw\|4alw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xqz\|1xqz]], [[1xr1\|1xr1]], [[1xws\|1xws]], [[1yhs\|1yhs]], [[1yi3\|1yi3]], [[1yi4\|1yi4]], [[1ywv\|1ywv]], [[1yxs\|1yxs]], [[1yxt\|1yxt]], [[1yxu\|1yxu]], [[1yxv\|1yxv]], [[1yxx\|1yxx]], [[2bik\|2bik]], [[2bil\|2bil]], [[2bzh\|2bzh]], [[2bzi\|2bzi]], [[2bzj\|2bzj]], [[2bzk\|2bzk]], [[2c3i\|2c3i]], [[2j2i\|2j2i]], [[2xix\|2xix]], [[2xiy\|2xiy]], [[2xiz\|2xiz]], [[2xj0\|2xj0]], [[2xj1\|2xj1]], [[2xj2\|2xj2]], [[4a7c\|4a7c]], [[4alu\|4alu]], [[4alv\|4alv]], [[4alw\|4alw]]</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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [http://www.ebi.ac.uk/pdbsum/4as0 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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [http://pdbe.org/4as0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [http://www.ebi.ac.uk/pdbsum/4as0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4as0 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 4as0" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Blanck, S]]		[[Category: Blanck, S]]

OCA at 22:52, 25 December 2014

OCA — Thu, 25 Dec 2014 22:52:33 GMT

←Older revision		Revision as of 22:52, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RPS:PHTALIMIDE-RUTHENIUM+COMPLEX'>RPS</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RPS:PHTALIMIDE-RUTHENIUM+COMPLEX'>RPS</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xqz\|1xqz]], [[1xr1\|1xr1]], [[1xws\|1xws]], [[1yhs\|1yhs]], [[1yi3\|1yi3]], [[1yi4\|1yi4]], [[1ywv\|1ywv]], [[1yxs\|1yxs]], [[1yxt\|1yxt]], [[1yxu\|1yxu]], [[1yxv\|1yxv]], [[1yxx\|1yxx]], [[2bik\|2bik]], [[2bil\|2bil]], [[2bzh\|2bzh]], [[2bzi\|2bzi]], [[2bzj\|2bzj]], [[2bzk\|2bzk]], [[2c3i\|2c3i]], [[2j2i\|2j2i]], [[2xix\|2xix]], [[2xiy\|2xiy]], [[2xiz\|2xiz]], [[2xj0\|2xj0]], [[2xj1\|2xj1]], [[2xj2\|2xj2]], [[4a7c\|4a7c]], [[4alu\|4alu]], [[4alv\|4alv]], [[4alw\|4alw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xqz\|1xqz]], [[1xr1\|1xr1]], [[1xws\|1xws]], [[1yhs\|1yhs]], [[1yi3\|1yi3]], [[1yi4\|1yi4]], [[1ywv\|1ywv]], [[1yxs\|1yxs]], [[1yxt\|1yxt]], [[1yxu\|1yxu]], [[1yxv\|1yxv]], [[1yxx\|1yxx]], [[2bik\|2bik]], [[2bil\|2bil]], [[2bzh\|2bzh]], [[2bzi\|2bzi]], [[2bzj\|2bzj]], [[2bzk\|2bzk]], [[2c3i\|2c3i]], [[2j2i\|2j2i]], [[2xix\|2xix]], [[2xiy\|2xiy]], [[2xiz\|2xiz]], [[2xj0\|2xj0]], [[2xj1\|2xj1]], [[2xj2\|2xj2]], [[4a7c\|4a7c]], [[4alu\|4alu]], [[4alv\|4alv]], [[4alw\|4alw]]</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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [http://www.ebi.ac.uk/pdbsum/4as0 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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [http://www.ebi.ac.uk/pdbsum/4as0 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 25:		Line 27:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Blanck, S.]]	+	[[Category: Blanck, S]]
-	[[Category: Essen, L O.]]	+	[[Category: Essen, L O]]
-	[[Category: Geisselbrecht, Y.]]	+	[[Category: Geisselbrecht, Y]]
-	[[Category: Harms, K.]]	+	[[Category: Harms, K]]
-	[[Category: Meggers, E.]]	+	[[Category: Meggers, E]]
-	[[Category: Middel, S.]]	+	[[Category: Middel, S]]
-	[[Category: Mietke, T.]]	+	[[Category: Mietke, T]]
	[[Category: Kinase inhibitor]]		[[Category: Kinase inhibitor]]
	[[Category: Octasporine]]		[[Category: Octasporine]]

OCA at 07:51, 9 July 2014

OCA — Wed, 09 Jul 2014 07:51:11 GMT

←Older revision		Revision as of 07:51, 9 July 2014
Line 1:		Line 1:
-	[[~~Image:~~4as0.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Cyclometalated Phthalimides as Protein Kinase Inhibitors==
		+	<StructureSection load='4as0' size='340' side='right' caption='[[4as0]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4as0]] 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=4AS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AS0 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RPS:PHTALIMIDE-RUTHENIUM+COMPLEX'>RPS</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xqz\|1xqz]], [[1xr1\|1xr1]], [[1xws\|1xws]], [[1yhs\|1yhs]], [[1yi3\|1yi3]], [[1yi4\|1yi4]], [[1ywv\|1ywv]], [[1yxs\|1yxs]], [[1yxt\|1yxt]], [[1yxu\|1yxu]], [[1yxv\|1yxv]], [[1yxx\|1yxx]], [[2bik\|2bik]], [[2bil\|2bil]], [[2bzh\|2bzh]], [[2bzi\|2bzi]], [[2bzj\|2bzj]], [[2bzk\|2bzk]], [[2c3i\|2c3i]], [[2j2i\|2j2i]], [[2xix\|2xix]], [[2xiy\|2xiy]], [[2xiz\|2xiz]], [[2xj0\|2xj0]], [[2xj1\|2xj1]], [[2xj2\|2xj2]], [[4a7c\|4a7c]], [[4alu\|4alu]], [[4alv\|4alv]], [[4alw\|4alw]]</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=4as0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4as0 RCSB], [http://www.ebi.ac.uk/pdbsum/4as0 PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The regioselective cyclometalation of 4-(pyridin-2-yl)phthalimide was exploited for the economical design of organometallic protein kinase inhibitors. 4-(Pyridin-2-yl)phthalimide can be prepared from inexpensive 4-bromophthalimide in just three steps including one Pd-catalyzed Stille cross-coupling. The versatility of this new ligand was demonstrated with the synthesis of ruthenium(II) half-sandwich as well as octahedral ruthenium(II) and iridium(III) complexes. The regioselectivity of the C-H activation in the course of the cyclometalation can be influenced by the reaction conditions and the steric demand of the introduced metal complex fragment. The biological activity of this new class of metalated phthalimides was evaluated by profiling two representative members against a large panel of human protein kinases. A cocrystal structure of one metallo-phthalimide with the protein kinase Pim1 confirmed an ATP-competitive binding with the intended hydrogen bonding between the phthalimide moiety and the hinge region of the ATP-binding site.

-	~~{{STRUCTURE_4as0\| PDB=4as0 \| SCENE= }}~~	+	Bioactive cyclometalated phthalimides: design, synthesis and kinase inhibition.,Blanck S, Geisselbrecht Y, Kraling K, Middel S, Mietke T, Harms K, Essen LO, Meggers E Dalton Trans. 2012 Aug 21;41(31):9337-48. Epub 2012 Jun 26. PMID:22733119<ref>PMID:22733119</ref>

-	~~===Cyclometalated Phthalimides as Protein Kinase Inhibitors===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22733119}}~~	+	==See Also==
-		+	*[[Proto-oncogene serine/threonine-protein kinase\|Proto-oncogene serine/threonine-protein kinase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~4as0]] 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=4AS0 OCA].~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 06:18, 3 October 2012

OCA — Wed, 03 Oct 2012 06:18:08 GMT

←Older revision		Revision as of 06:18, 3 October 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4as0.jpg\|left\|200px]]

-	~~The entry~~ 4as0 ~~is ON HOLD~~	+	{{STRUCTURE_4as0\| PDB=4as0 \| SCENE= }}

-	~~Authors: Blanck, S., Geisselbrecht, Y., Middel, S., Mietke, T., Harms, K., Essen, L.-O., Meggers, E.~~	+	===Cyclometalated Phthalimides as Protein Kinase Inhibitors===

-	~~Description~~: ~~Cyclometalated Phthalimides as Protein~~ Kinase ~~Inhibitors~~	+	{{ABSTRACT_PUBMED_22733119}}
		+
		+	==About this Structure==
		+	[[4as0]] 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=4AS0 OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Blanck, S.]]
		+	[[Category: Essen, L O.]]
		+	[[Category: Geisselbrecht, Y.]]
		+	[[Category: Harms, K.]]
		+	[[Category: Meggers, E.]]
		+	[[Category: Middel, S.]]
		+	[[Category: Mietke, T.]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Octasporine]]
		+	[[Category: Pim1]]
		+	[[Category: Ruthenium]]
		+	[[Category: Transferase]]

OCA at 08:41, 9 May 2012

OCA — Wed, 09 May 2012 08:41:35 GMT

←Older revision		Revision as of 08:41, 9 May 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4as0 is ON HOLD ~~until sometime in the future~~	+	The entry 4as0 is ON HOLD

	Authors: Blanck, S., Geisselbrecht, Y., Middel, S., Mietke, T., Harms, K., Essen, L.-O., Meggers, E.		Authors: Blanck, S., Geisselbrecht, Y., Middel, S., Mietke, T., Harms, K., Essen, L.-O., Meggers, E.

	Description: Cyclometalated Phthalimides as Protein Kinase Inhibitors		Description: Cyclometalated Phthalimides as Protein Kinase Inhibitors

OCA: Protected "4as0" [edit=sysop:move=sysop]

OCA — Wed, 02 May 2012 18:50:47 GMT

Protected "4as0" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:50, 2 May 2012

OCA: New page: '''Unreleased structure''' The entry 4as0 is ON HOLD until sometime in the future Authors: Blanck, S., Geisselbrecht, Y., Middel, S., Mietke, T., Harms, K., Essen, L.-O., Meggers, E. D...

OCA — Wed, 02 May 2012 18:50:46 GMT

New page: '''Unreleased structure''' The entry 4as0 is ON HOLD until sometime in the future Authors: Blanck, S., Geisselbrecht, Y., Middel, S., Mietke, T., Harms, K., Essen, L.-O., Meggers, E. D...

New page

'''Unreleased structure'''

The entry 4as0 is ON HOLD until sometime in the future

Authors: Blanck, S., Geisselbrecht, Y., Middel, S., Mietke, T., Harms, K., Essen, L.-O., Meggers, E.

Description: Cyclometalated Phthalimides as Protein Kinase Inhibitors