3zrl - Revision history

OCA at 11:10, 20 December 2023

OCA — Wed, 20 Dec 2023 11:10:45 GMT

←Older revision		Revision as of 11:10, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='3zrl' size='340' side='right'caption='[[3zrl]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='3zrl' size='340' side='right'caption='[[3zrl]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>~~, ~~<scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO~~[3,2~~-C]PYRIDIN-4-ONE'>ZRL</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]] 2.48Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~PTR~~:~~O-PHOSPHOTYROSINE~~'>~~PTR~~</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO[3,2-C]PYRIDIN-4-ONE'>ZRL</scene></td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat"><div style='overflow: auto; max~~-~~height: 3em;~~'>[[2uw9\|2uw9]], [[1o6k\|1o6k]], [[1gng\|1gng]], [[1h8f\|1h8f]], [[1q3w\|1q3w]], [[3zrk\|3zrk]], [[1i09\|1i09]], [[1o9u\|1o9u]], [[2x37\|2x37]], [[2jdr\|2jdr]], [[1o6l\|1o6l]], [[1j1b\|1j1b]], [[1r0e\|1r0e]], [[2x39\|2x39]], [[1q41\|1q41]], [[1q3d\|1q3d]], [[2jld\|2jld]], [[1q5k\|1q5k]], [[2jdo\|2jdo]], [[1pyx\|1pyx]], [[1q4l\|1q4l]], [[1j1c\|1j1c]], [[2xh5\|2xh5]], [[1uv5\|1uv5]], [[3zrm\|3zrm]]</~~div~~><~~/td></tr>~~	+
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class="sblockDat"><span class~~='~~plainlinks'>[https~~:~~//en.wikipedia.org/wiki/~~[~~Tau_protein]_kinase [Tau protein] kinase]~~, ~~with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26~~] </~~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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [https://pdbe.org/3zrl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [https://www.ebi.ac.uk/pdbsum/3zrl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zrl 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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [https://pdbe.org/3zrl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [https://www.ebi.ac.uk/pdbsum/3zrl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zrl ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/GSK3B_HUMAN GSK3B_HUMAN]] Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation.<ref>PMID:1846781</ref> <ref>PMID:8397507</ref> <ref>PMID:9072970</ref> <ref>PMID:9819408</ref> <ref>PMID:11430833</ref> <ref>PMID:14690523</ref> <ref>PMID:15448698</ref> <ref>PMID:18348280</ref> <ref>PMID:20932480</ref> <ref>PMID:20937854</ref> <ref>PMID:22514281</ref> <ref>PMID:12554650</ref> [[https://www.uniprot.org/uniprot/FRAT1_HUMAN FRAT1_HUMAN]] Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3. May play a role in tumor progression and collaborate with PIM1 and MYC in lymphomagenesis.<ref>PMID:12556519</ref>	+	[https://www.uniprot.org/uniprot/GSK3B_HUMAN GSK3B_HUMAN] Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation.<ref>PMID:1846781</ref> <ref>PMID:8397507</ref> <ref>PMID:9072970</ref> <ref>PMID:9819408</ref> <ref>PMID:11430833</ref> <ref>PMID:14690523</ref> <ref>PMID:15448698</ref> <ref>PMID:18348280</ref> <ref>PMID:20932480</ref> <ref>PMID:20937854</ref> <ref>PMID:22514281</ref> <ref>PMID:12554650</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bamborough, P]]	+	[[Category: Bamborough P]]
-	[[Category: Bax, B]]	+	[[Category: Bax B]]
-	[[Category: Bernasconi, G]]	+	[[Category: Bernasconi G]]
-	[[Category: Bridges, A]]	+	[[Category: Bridges A]]
-	[[Category: Brough, C]]	+	[[Category: Brough C]]
-	[[Category: Carter, P]]	+	[[Category: Carter P]]
-	[[Category: Cutler, G]]	+	[[Category: Cutler G]]
-	[[Category: Gentile, G]]	+	[[Category: Gentile G]]
-	[[Category: Marzorati, P]]	+	[[Category: Marzorati P]]
-	[[Category: Merlo, G]]	+	[[Category: Merlo G]]
-	[[Category: Neu, M]]	+	[[Category: Neu M]]
-	[[Category: Pozzan, A]]	+	[[Category: Pozzan A]]
-	[[Category: Takada, M]]	+	[[Category: Takada M]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-peptide complex~~]]	+

OCA at 07:12, 18 August 2022

OCA — Thu, 18 Aug 2022 07:12:35 GMT

←Older revision		Revision as of 07:12, 18 August 2022
Line 1:		Line 1:

	==Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors==		==Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors==
-	<StructureSection load='3zrl' size='340' side='right' caption='[[3zrl]], [[Resolution\|resolution]] 2.48Å' scene=''>	+	<StructureSection load='3zrl' size='340' side='right'caption='[[3zrl]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO[3,2-C]PYRIDIN-4-ONE'>ZRL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO[3,2-C]PYRIDIN-4-ONE'>ZRL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2uw9\|2uw9]], [[1o6k\|1o6k]], [[1gng\|1gng]], [[1h8f\|1h8f]], [[1q3w\|1q3w]], [[3zrk\|3zrk]], [[1i09\|1i09]], [[1o9u\|1o9u]], [[2x37\|2x37]], [[2jdr\|2jdr]], [[1o6l\|1o6l]], [[1j1b\|1j1b]], [[1r0e\|1r0e]], [[2x39\|2x39]], [[1q41\|1q41]], [[1q3d\|1q3d]], [[2jld\|2jld]], [[1q5k\|1q5k]], [[2jdo\|2jdo]], [[1pyx\|1pyx]], [[1q4l\|1q4l]], [[1j1c\|1j1c]], [[2xh5\|2xh5]], [[1uv5\|1uv5]], [[3zrm\|3zrm]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2uw9\|2uw9]], [[1o6k\|1o6k]], [[1gng\|1gng]], [[1h8f\|1h8f]], [[1q3w\|1q3w]], [[3zrk\|3zrk]], [[1i09\|1i09]], [[1o9u\|1o9u]], [[2x37\|2x37]], [[2jdr\|2jdr]], [[1o6l\|1o6l]], [[1j1b\|1j1b]], [[1r0e\|1r0e]], [[2x39\|2x39]], [[1q41\|1q41]], [[1q3d\|1q3d]], [[2jld\|2jld]], [[1q5k\|1q5k]], [[2jdo\|2jdo]], [[1pyx\|1pyx]], [[1q4l\|1q4l]], [[1j1c\|1j1c]], [[2xh5\|2xh5]], [[1uv5\|1uv5]], [[3zrm\|3zrm]]</div></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/[Tau_protein]_kinase [Tau protein] kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/[Tau_protein]_kinase [Tau protein] kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26] </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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [~~http~~://pdbe.org/3zrl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3zrl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3zrl 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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [https://pdbe.org/3zrl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [https://www.ebi.ac.uk/pdbsum/3zrl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zrl ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/GSK3B_HUMAN GSK3B_HUMAN]] Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation.<ref>PMID:1846781</ref> <ref>PMID:8397507</ref> <ref>PMID:9072970</ref> <ref>PMID:9819408</ref> <ref>PMID:11430833</ref> <ref>PMID:14690523</ref> <ref>PMID:15448698</ref> <ref>PMID:18348280</ref> <ref>PMID:20932480</ref> <ref>PMID:20937854</ref> <ref>PMID:22514281</ref> <ref>PMID:12554650</ref> [[~~http~~://www.uniprot.org/uniprot/FRAT1_HUMAN FRAT1_HUMAN]] Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3. May play a role in tumor progression and collaborate with PIM1 and MYC in lymphomagenesis.<ref>PMID:12556519</ref>	+	[[https://www.uniprot.org/uniprot/GSK3B_HUMAN GSK3B_HUMAN]] Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation.<ref>PMID:1846781</ref> <ref>PMID:8397507</ref> <ref>PMID:9072970</ref> <ref>PMID:9819408</ref> <ref>PMID:11430833</ref> <ref>PMID:14690523</ref> <ref>PMID:15448698</ref> <ref>PMID:18348280</ref> <ref>PMID:20932480</ref> <ref>PMID:20937854</ref> <ref>PMID:22514281</ref> <ref>PMID:12554650</ref> [[https://www.uniprot.org/uniprot/FRAT1_HUMAN FRAT1_HUMAN]] Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3. May play a role in tumor progression and collaborate with PIM1 and MYC in lymphomagenesis.<ref>PMID:12556519</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:

	==See Also==		==See Also==
-	*[[Glycogen synthase kinase 3\|Glycogen synthase kinase 3]]	+	*[[Glycogen synthase kinase 3 3D structures\|Glycogen synthase kinase 3 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bamborough, P]]		[[Category: Bamborough, P]]
	[[Category: Bax, B]]		[[Category: Bax, B]]

OCA at 07:45, 4 August 2016

OCA — Thu, 04 Aug 2016 07:45:14 GMT

←Older revision		Revision as of 07:45, 4 August 2016
Line 1:		Line 1:
		+
	==Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors==		==Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors==
	<StructureSection load='3zrl' size='340' side='right' caption='[[3zrl]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='3zrl' size='340' side='right' caption='[[3zrl]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO[3,2-C]PYRIDIN-4-ONE'>ZRL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO[3,2-C]PYRIDIN-4-ONE'>ZRL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2uw9\|2uw9]], [[1o6k\|1o6k]], [[1gng\|1gng]], [[1h8f\|1h8f]], [[1q3w\|1q3w]], [[3zrk\|3zrk]], [[1i09\|1i09]], [[1o9u\|1o9u]], [[2x37\|2x37]], [[2jdr\|2jdr]], [[1o6l\|1o6l]], [[1j1b\|1j1b]], [[1r0e\|1r0e]], [[2x39\|2x39]], [[1q41\|1q41]], [[1q3d\|1q3d]], [[2jld\|2jld]], [[1q5k\|1q5k]], [[2jdo\|2jdo]], [[1pyx\|1pyx]], [[1q4l\|1q4l]], [[1j1c\|1j1c]], [[2xh5\|2xh5]], [[1uv5\|1uv5]], [[3zrm\|3zrm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2uw9\|2uw9]], [[1o6k\|1o6k]], [[1gng\|1gng]], [[1h8f\|1h8f]], [[1q3w\|1q3w]], [[3zrk\|3zrk]], [[1i09\|1i09]], [[1o9u\|1o9u]], [[2x37\|2x37]], [[2jdr\|2jdr]], [[1o6l\|1o6l]], [[1j1b\|1j1b]], [[1r0e\|1r0e]], [[2x39\|2x39]], [[1q41\|1q41]], [[1q3d\|1q3d]], [[2jld\|2jld]], [[1q5k\|1q5k]], [[2jdo\|2jdo]], [[1pyx\|1pyx]], [[1q4l\|1q4l]], [[1j1c\|1j1c]], [[2xh5\|2xh5]], [[1uv5\|1uv5]], [[3zrm\|3zrm]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Tau_protein]_kinase [Tau protein] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Tau_protein]_kinase [Tau protein] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26] </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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [http://www.ebi.ac.uk/pdbsum/3zrl 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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [http://pdbe.org/3zrl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [http://www.ebi.ac.uk/pdbsum/3zrl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zrl ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 3zrl" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Bamborough, P]]		[[Category: Bamborough, P]]
	[[Category: Bax, B]]		[[Category: Bax, B]]

OCA at 07:09, 24 December 2014

OCA — Wed, 24 Dec 2014 07:09:27 GMT

←Older revision		Revision as of 07:09, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>		<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO[3,2-C]PYRIDIN-4-ONE'>ZRL</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO[3,2-C]PYRIDIN-4-ONE'>ZRL</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2uw9\|2uw9]], [[1o6k\|1o6k]], [[1gng\|1gng]], [[1h8f\|1h8f]], [[1q3w\|1q3w]], [[3zrk\|3zrk]], [[1i09\|1i09]], [[1o9u\|1o9u]], [[2x37\|2x37]], [[2jdr\|2jdr]], [[1o6l\|1o6l]], [[1j1b\|1j1b]], [[1r0e\|1r0e]], [[2x39\|2x39]], [[1q41\|1q41]], [[1q3d\|1q3d]], [[2jld\|2jld]], [[1q5k\|1q5k]], [[2jdo\|2jdo]], [[1pyx\|1pyx]], [[1q4l\|1q4l]], [[1j1c\|1j1c]], [[2xh5\|2xh5]], [[1uv5\|1uv5]], [[3zrm\|3zrm]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2uw9\|2uw9]], [[1o6k\|1o6k]], [[1gng\|1gng]], [[1h8f\|1h8f]], [[1q3w\|1q3w]], [[3zrk\|3zrk]], [[1i09\|1i09]], [[1o9u\|1o9u]], [[2x37\|2x37]], [[2jdr\|2jdr]], [[1o6l\|1o6l]], [[1j1b\|1j1b]], [[1r0e\|1r0e]], [[2x39\|2x39]], [[1q41\|1q41]], [[1q3d\|1q3d]], [[2jld\|2jld]], [[1q5k\|1q5k]], [[2jdo\|2jdo]], [[1pyx\|1pyx]], [[1q4l\|1q4l]], [[1j1c\|1j1c]], [[2xh5\|2xh5]], [[1uv5\|1uv5]], [[3zrm\|3zrm]]</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Tau_protein]_kinase [Tau protein] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Tau_protein]_kinase [Tau protein] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26] </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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [http://www.ebi.ac.uk/pdbsum/3zrl 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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [http://www.ebi.ac.uk/pdbsum/3zrl PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GSK3B_HUMAN GSK3B_HUMAN]] Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation.<ref>PMID:1846781</ref> <ref>PMID:8397507</ref> <ref>PMID:9072970</ref> <ref>PMID:9819408</ref> <ref>PMID:11430833</ref> <ref>PMID:14690523</ref> <ref>PMID:15448698</ref> <ref>PMID:18348280</ref> <ref>PMID:20932480</ref> <ref>PMID:20937854</ref> <ref>PMID:22514281</ref> <ref>PMID:12554650</ref> [[http://www.uniprot.org/uniprot/FRAT1_HUMAN FRAT1_HUMAN]] Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3. May play a role in tumor progression and collaborate with PIM1 and MYC in lymphomagenesis.<ref>PMID:12556519</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Bamborough, P.]]	+	[[Category: Bamborough, P]]
-	[[Category: Bax, B.]]	+	[[Category: Bax, B]]
-	[[Category: Bernasconi, G.]]	+	[[Category: Bernasconi, G]]
-	[[Category: Bridges, A.]]	+	[[Category: Bridges, A]]
-	[[Category: Brough, C.]]	+	[[Category: Brough, C]]
-	[[Category: Carter, P.]]	+	[[Category: Carter, P]]
-	[[Category: Cutler, G.]]	+	[[Category: Cutler, G]]
-	[[Category: Gentile, G.]]	+	[[Category: Gentile, G]]
-	[[Category: Marzorati, P.]]	+	[[Category: Marzorati, P]]
-	[[Category: Merlo, G.]]	+	[[Category: Merlo, G]]
-	[[Category: Neu, M.]]	+	[[Category: Neu, M]]
-	[[Category: Pozzan, A.]]	+	[[Category: Pozzan, A]]
-	[[Category: Takada, M.]]	+	[[Category: Takada, M]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase-peptide complex]]		[[Category: Transferase-peptide complex]]

OCA at 07:42, 5 June 2014

OCA — Thu, 05 Jun 2014 07:42:01 GMT

←Older revision		Revision as of 07:42, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~3zrl.~~png~~\|~~left~~\|~~200px~~]]	+	==Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors==
		+	<StructureSection load='3zrl' size='340' side='right' caption='[[3zrl]], [[Resolution\|resolution]] 2.48Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3zrl]] is a 4 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=3ZRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZRL FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZRL:7-BROMO-2-PYRIDIN-4-YL-5H-THIENO[3,2-C]PYRIDIN-4-ONE'>ZRL</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2uw9\|2uw9]], [[1o6k\|1o6k]], [[1gng\|1gng]], [[1h8f\|1h8f]], [[1q3w\|1q3w]], [[3zrk\|3zrk]], [[1i09\|1i09]], [[1o9u\|1o9u]], [[2x37\|2x37]], [[2jdr\|2jdr]], [[1o6l\|1o6l]], [[1j1b\|1j1b]], [[1r0e\|1r0e]], [[2x39\|2x39]], [[1q41\|1q41]], [[1q3d\|1q3d]], [[2jld\|2jld]], [[1q5k\|1q5k]], [[2jdo\|2jdo]], [[1pyx\|1pyx]], [[1q4l\|1q4l]], [[1j1c\|1j1c]], [[2xh5\|2xh5]], [[1uv5\|1uv5]], [[3zrm\|3zrm]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Tau_protein]_kinase [Tau protein] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.26 2.7.11.26] </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=3zrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zrl RCSB], [http://www.ebi.ac.uk/pdbsum/3zrl PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The discovery of a novel series of 2-(4-pyridyl)thienopyridinone GSK-3beta inhibitors is reported. X-ray crystallography reveals its binding mode and enables rationalization of the SAR. The initial optimization of the template for improved cellular activity and predicted CNS penetration is also presented.

-	<!--	+	Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors.,Gentile G, Bernasconi G, Pozzan A, Merlo G, Marzorati P, Bamborough P, Bax B, Bridges A, Brough C, Carter P, Cutler G, Neu M, Takada M Bioorg Med Chem Lett. 2011 Aug 15;21(16):4823-7. Epub 2011 Jun 29. PMID:21764580<ref>PMID:21764580</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3zrl"~~, ~~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_3zrl\| PDB=3zrl \| SCENE= }}~~	+

-	~~===Identification~~ of ~~2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	~~<!--~~	+	*[[Glycogen synthase kinase 3\|Glycogen synthase kinase 3]]
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21764580}}, adds the Publication Abstract to the page~~	+	== References ==
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 21764580 is the PubMed ID number.~~	+	<references/>
-	~~-->~~	+	__TOC__
-	~~{{ABSTRACT_PUBMED_21764580}}~~	+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[~~3zrl~~]] is a 4 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=3ZRL OCA].	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:021764580<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bamborough, P.]]		[[Category: Bamborough, P.]]

OCA at 08:22, 25 April 2012

OCA — Wed, 25 Apr 2012 08:22:06 GMT

←Older revision		Revision as of 08:22, 25 April 2012
Line 1:		Line 1:
-	[[Image:3zrl.~~jpg~~\|left\|200px]]	+	[[Image:3zrl.png\|left\|200px]]

	<!--		<!--
Line 9:		Line 9:
	{{STRUCTURE_3zrl\| PDB=3zrl \| SCENE= }}		{{STRUCTURE_3zrl\| PDB=3zrl \| SCENE= }}

-	===~~IDENTIFICATION OF~~ 2-(4-~~PYRIDYL~~)~~THIENOPYRIDINONES AS~~ GSK-~~3BETA INHIBITORS~~===	+	===Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21764580}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21764580 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21764580}}

	==About this Structure==		==About this Structure==
	[[3zrl]] is a 4 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=3ZRL OCA].		[[3zrl]] is a 4 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=3ZRL OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021764580</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bamborough, P.]]		[[Category: Bamborough, P.]]

OCA at 06:28, 29 June 2011

OCA — Wed, 29 Jun 2011 06:28:30 GMT

←Older revision		Revision as of 06:28, 29 June 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3zrl.jpg\|left\|200px]]

-	The ~~entry 3zrl~~ is ~~ON HOLD until sometime in~~ the ~~future~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3zrl", 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_3zrl\| PDB=3zrl \| SCENE= }}

-	~~Authors: Gentile, G., Bernasconi, G., Pozzan, A., Merlo, G., Marzorati, P., Bamborough, P., Bax, B., Bridges, A., Brough, C., Carter, P., Cutler, G., Neu, M., Takada, M.~~	+	===IDENTIFICATION OF 2-(4-PYRIDYL)THIENOPYRIDINONES AS GSK-3BETA INHIBITORS===

-	~~Description~~: ~~Identification of 2~~-~~(4-pyridyl)thienopyridinones as GSK~~-~~3beta inhibitors~~	+
		+	==About this Structure==
		+	[[3zrl]] is a 4 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=3ZRL OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Bamborough, P.]]
		+	[[Category: Bax, B.]]
		+	[[Category: Bernasconi, G.]]
		+	[[Category: Bridges, A.]]
		+	[[Category: Brough, C.]]
		+	[[Category: Carter, P.]]
		+	[[Category: Cutler, G.]]
		+	[[Category: Gentile, G.]]
		+	[[Category: Marzorati, P.]]
		+	[[Category: Merlo, G.]]
		+	[[Category: Neu, M.]]
		+	[[Category: Pozzan, A.]]
		+	[[Category: Takada, M.]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-peptide complex]]

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

OCA — Wed, 22 Jun 2011 16:26:42 GMT

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

←Older revision

Revision as of 16:26, 22 June 2011

OCA: New page: '''Unreleased structure''' The entry 3zrl is ON HOLD until sometime in the future Authors: Gentile, G., Bernasconi, G., Pozzan, A., Merlo, G., Marzorati, P., Bamborough, P., Bax, B., Br...

OCA — Wed, 22 Jun 2011 16:26:41 GMT

New page: '''Unreleased structure''' The entry 3zrl is ON HOLD until sometime in the future Authors: Gentile, G., Bernasconi, G., Pozzan, A., Merlo, G., Marzorati, P., Bamborough, P., Bax, B., Br...

New page

'''Unreleased structure'''

The entry 3zrl is ON HOLD until sometime in the future

Authors: Gentile, G., Bernasconi, G., Pozzan, A., Merlo, G., Marzorati, P., Bamborough, P., Bax, B., Bridges, A., Brough, C., Carter, P., Cutler, G., Neu, M., Takada, M.

Description: Identification of 2-(4-pyridyl)thienopyridinones as GSK-3beta inhibitors