6ayd - Revision history

OCA at 14:28, 4 October 2023

OCA — Wed, 04 Oct 2023 14:28:39 GMT

←Older revision		Revision as of 14:28, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6ayd' size='340' side='right'caption='[[6ayd]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='6ayd' size='340' side='right'caption='[[6ayd]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ayd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6AYD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ayd]] 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=6AYD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AYD FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=C2J:N~~-[~~6-(4-hydroxyphenyl)-2H-indazol-~~3~~-yl]cyclopropanecarboxamide'>C2J</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]] 3Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C2J:N-[6-(4-hydroxyphenyl)-2H-indazol-3-yl]cyclopropanecarboxamide'>C2J</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6ayd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayd OCA], [~~http~~://pdbe.org/6ayd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ayd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ayd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayd 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=6ayd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayd OCA], [https://pdbe.org/6ayd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ayd RCSB], [https://www.ebi.ac.uk/pdbsum/6ayd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayd 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 27:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Henley ZA]]
-	[[Category: Henley~~, Z A~~]]	+	[[Category: Shewchuk LM]]
-	[[Category: Shewchuk~~, L M]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 21:34, 28 October 2020

OCA — Wed, 28 Oct 2020 21:34:03 GMT

←Older revision		Revision as of 21:34, 28 October 2020
Line 1:		Line 1:

	==Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-yl)cyclopropanecarboxamide==		==Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-yl)cyclopropanecarboxamide==
-	<StructureSection load='6ayd' size='340' side='right' caption='[[6ayd]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='6ayd' size='340' side='right'caption='[[6ayd]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ayd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYD OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AYD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ayd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6AYD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C2J:N-[6-(4-hydroxyphenyl)-2H-indazol-3-yl]cyclopropanecarboxamide'>C2J</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C2J:N-[6-(4-hydroxyphenyl)-2H-indazol-3-yl]cyclopropanecarboxamide'>C2J</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6ayd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayd OCA], [http://pdbe.org/6ayd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ayd RCSB], [http://www.ebi.ac.uk/pdbsum/6ayd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayd ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ayd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayd OCA], [http://pdbe.org/6ayd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ayd RCSB], [http://www.ebi.ac.uk/pdbsum/6ayd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6ayd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ayd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
		+	*[[3D structures of pim-1\|3D structures of pim-1]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Henley, Z A]]		[[Category: Henley, Z A]]

OCA at 08:36, 27 December 2017

OCA — Wed, 27 Dec 2017 08:36:26 GMT

←Older revision		Revision as of 08:36, 27 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ayd is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-yl)cyclopropanecarboxamide==
		+	<StructureSection load='6ayd' size='340' side='right' caption='[[6ayd]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ayd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AYD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C2J:N-[6-(4-hydroxyphenyl)-2H-indazol-3-yl]cyclopropanecarboxamide'>C2J</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ayd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayd OCA], [http://pdbe.org/6ayd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ayd RCSB], [http://www.ebi.ac.uk/pdbsum/6ayd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayd ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Selective inhibitors of phosphoinositide 3-kinase delta are of interest for the treatment of inflammatory diseases. Initial optimization of a 3-substituted indazole hit compound targeting the kinase PIM1 focused on improving selectivity over GSK3beta through consideration of differences in the ATP binding pockets. Continued kinase cross-screening showed PI3Kdelta activity in a series of 4,6-disubstituted indazole compounds, and subsequent structure-activity relationship exploration led to the discovery of an indole-containing lead compound as a potent PI3Kdelta inhibitor with selectivity over the other PI3K isoforms.

-	~~Authors~~: ~~Shewchuk, L.M~~., Henley, Z.A.	+	From PIM1 to PI3Kdelta via GSK3beta: Target Hopping through the Kinome.,Henley ZA, Bax BD, Inglesby LM, Champigny A, Gaines S, Faulder P, Le J, Thomas DA, Washio Y, Baldwin IR ACS Med Chem Lett. 2017 Sep 7;8(10):1093-1098. doi:, 10.1021/acsmedchemlett.7b00296. eCollection 2017 Oct 12. PMID:29057057<ref>PMID:29057057</ref>

-	~~Description: Pim1 complexed with N-(6-(4~~-~~hydroxyphenyl)~~-~~1H-indazol-3-yl)cyclopropanecarboxamide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Henley, Z.A]]	+	<div class="pdbe-citations 6ayd" style="background-color:#fffaf0;"></div>
-	[[Category: Shewchuk, L.M]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Henley, Z A]]
		+	[[Category: Shewchuk, L M]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "6ayd" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 16:57:18 GMT

Protected "6ayd" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:57, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6ayd is ON HOLD until Paper Publication Authors: Shewchuk, L.M., Henley, Z.A. Description: Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-...

OCA — Wed, 27 Sep 2017 16:57:17 GMT

New page: '''Unreleased structure''' The entry 6ayd is ON HOLD until Paper Publication Authors: Shewchuk, L.M., Henley, Z.A. Description: Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-...

New page

'''Unreleased structure'''

The entry 6ayd is ON HOLD until Paper Publication

Authors: Shewchuk, L.M., Henley, Z.A.

Description: Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-yl)cyclopropanecarboxamide
[[Category: Unreleased Structures]]
[[Category: Henley, Z.A]]
[[Category: Shewchuk, L.M]]