3tti - Revision history

OCA at 10:11, 1 March 2024

2024-03-01T10:11:26Z

← Older revision		Revision as of 10:11, 1 March 2024
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	<StructureSection load='3tti' size='340' side='right'caption='[[3tti]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3tti' size='340' side='right'caption='[[3tti]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tti]] 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=3TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TTI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tti]] 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=3TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TTI 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=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</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]] 2.2Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ttj\|3ttj]]</div></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=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JNK3, JNK3A, MAPK10, PRKM10 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [https://pdbe.org/3tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [https://www.ebi.ac.uk/pdbsum/3tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tti 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=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [https://pdbe.org/3tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [https://www.ebi.ac.uk/pdbsum/3tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tti ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[https://omim.org/entry/606369 606369]]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.		[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[https://omim.org/entry/606369 606369]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</ref>		[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.

	Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor.,Plantevin Krenitsky V, Nadolny L, Delgado M, Ayala L, Clareen SS, Hilgraf R, Albers R, Hegde S, D'Sidocky N, Sapienza J, Wright J, McCarrick M, Bahmanyar S, Chamberlain P, Delker SL, Muir J, Giegel D, Xu L, Celeridad M, Lachowitzer J, Bennett B, Moghaddam M, Khatsenko O, Katz J, Fan R, Bai A, Tang Y, Shirley MA, Benish B, Bodine T, Blease K, Raymon H, Cathers BE, Satoh Y Bioorg Med Chem Lett. 2012 Feb 1;22(3):1433-8. Epub 2011 Dec 10. PMID:22244937<ref>PMID:22244937</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3tti" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Mitogen-activated protein kinase]]~~		[[Category: Albers R]]
	[[Category: Albers, R]]		[[Category: Ayala L]]
	[[Category: Ayala, L]]		[[Category: Bahmanyar S]]
	[[Category: Bahmanyar, S]]		[[Category: Bai A]]
	[[Category: Bai, A]]		[[Category: Benish B]]
	[[Category: Benish, B]]		[[Category: Bennett B]]
	[[Category: Bennett, B]]		[[Category: Blease K]]
	[[Category: Blease, K]]		[[Category: Bodine T]]
	[[Category: Bodine, T]]		[[Category: Cathers BE]]
	[[Category: Cathers~~, B E~~]]		[[Category: Celeridad M]]
	[[Category: Celeridad, M]]		[[Category: Chamberlain P]]
	[[Category: Chamberlain, P]]		[[Category: Clareen S]]
	[[Category: Clareen, S]]		[[Category: D'Sidocky N]]
	[[Category: Delgado, M]]		[[Category: Delgado M]]
	[[Category: Delker~~, S L~~]]		[[Category: Delker SL]]
	[[Category: Fan, R]]		[[Category: Fan R]]
	[[Category: Giegel, D]]		[[Category: Giegel D]]
	[[Category: Hegde, S]]		[[Category: Hegde S]]
	[[Category: Hilgraf, R]]		[[Category: Hilgraf R]]
	[[Category: Katz, J]]		[[Category: Katz J]]
	[[Category: Khatsenko, O]]		[[Category: Khatsenko O]]
	[[Category: Lachowitzer, J]]		[[Category: Lachowitzer J]]
	[[Category: McCarrick, M]]		[[Category: McCarrick M]]
	[[Category: Moghaddam, M]]		[[Category: Moghaddam M]]
	[[Category: Muir, J]]		[[Category: Muir J]]
	[[Category: Nadolny, L]]		[[Category: Nadolny L]]
	[[Category: Plantevin-Krenitsky, V]]		[[Category: Plantevin-Krenitsky V]]
	[[Category: Raymon, H]]		[[Category: Raymon H]]
	[[Category: Sapienza, J]]		[[Category: Sapienza J]]
	[[Category: Satoh, Y]]		[[Category: Satoh Y]]
	[[Category: Shirley~~, M A]]~~		[[Category: Shirley MA]]
	~~[[Category: Sidocky, N D~~]]		[[Category: Tang Y]]
	[[Category: Tang, Y]]		[[Category: Wright J]]
	[[Category: Wright, J]]		[[Category: Xu L]]
	[[Category: Xu, L]]
	~~[[Category: Jnk3]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Mitogen-activated protein kinase 10]]~~
	~~[[Category: Protein kinase inhibitor]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 05:44, 13 July 2022

2022-07-13T05:44:31Z

← Older revision		Revision as of 05:44, 13 July 2022
Line 1:		Line 1:

	==Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor==		==Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor==
	<StructureSection load='3tti' size='340' side='right' caption='[[3tti]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3tti' size='340' side='right'caption='[[3tti]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tti]] 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=3TTI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TTI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tti]] 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=3TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TTI 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=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</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=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ttj\|3ttj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ttj\|3ttj]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JNK3, JNK3A, MAPK10, PRKM10 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JNK3, JNK3A, MAPK10, PRKM10 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [~~http~~://pdbe.org/3tti PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tti PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tti 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=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [https://pdbe.org/3tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [https://www.ebi.ac.uk/pdbsum/3tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tti ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[~~http~~://omim.org/entry/606369 606369]]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.		[[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[https://omim.org/entry/606369 606369]]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</ref>		[[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 3tti" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3tti" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Mitogen-activated protein kinase 3D structures\|Mitogen-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
	[[Category: Albers, R]]		[[Category: Albers, R]]

OCA at 09:56, 8 November 2017

2017-11-08T09:56:30Z

← Older revision		Revision as of 09:56, 8 November 2017
Line 23:		Line 23:
	</div>		</div>
	<div class="pdbe-citations 3tti" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3tti" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:52, 11 August 2016

2016-08-11T07:52:27Z

← Older revision		Revision as of 07:52, 11 August 2016
Line 1:		Line 1:

	==Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor==		==Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor==
	<StructureSection load='3tti' size='340' side='right' caption='[[3tti]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3tti' size='340' side='right' caption='[[3tti]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tti]] 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=3TTI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TTI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tti]] 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=3TTI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TTI 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=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</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=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ttj\|3ttj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ttj\|3ttj]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JNK3, JNK3A, MAPK10, PRKM10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JNK3, JNK3A, MAPK10, PRKM10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [http://www.ebi.ac.uk/pdbsum/3tti 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=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [http://pdbe.org/3tti PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [http://www.ebi.ac.uk/pdbsum/3tti PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tti ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 3tti" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
	[[Category: Albers, R]]		[[Category: Albers, R]]

OCA at 14:50, 5 January 2015

2015-01-05T14:50:17Z

← Older revision		Revision as of 14:50, 5 January 2015
Line 1:		Line 1:
	~~{{STRUCTURE_3tti\| PDB=3tti \| SCENE= }}~~		==Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor==
	===Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor===		<StructureSection load='3tti' size='340' side='right' caption='[[3tti]], [[Resolution\|resolution]] 2.20Å' scene=''>
	{~~{ABSTRACT_PUBMED_22244937}~~}		== Structural highlights ==
			<table><tr><td colspan='2'>[[3tti]] 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=3TTI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TTI FirstGlance]. <br>
	==Disease==		</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=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ttj\|3ttj]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JNK3, JNK3A, MAPK10, PRKM10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [http://www.ebi.ac.uk/pdbsum/3tti PDBsum]</span></td></tr>
			</table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[http://omim.org/entry/606369 606369]]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.		[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[http://omim.org/entry/606369 606369]]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
			== Function ==
			[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.

	~~==Function==~~		Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor.,Plantevin Krenitsky V, Nadolny L, Delgado M, Ayala L, Clareen SS, Hilgraf R, Albers R, Hegde S, D'Sidocky N, Sapienza J, Wright J, McCarrick M, Bahmanyar S, Chamberlain P, Delker SL, Muir J, Giegel D, Xu L, Celeridad M, Lachowitzer J, Bennett B, Moghaddam M, Khatsenko O, Katz J, Fan R, Bai A, Tang Y, Shirley MA, Benish B, Bodine T, Blease K, Raymon H, Cathers BE, Satoh Y Bioorg Med Chem Lett. 2012 Feb 1;22(3):1433-8. Epub 2011 Dec 10. PMID:22244937<ref>PMID:22244937</ref>
	~~[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Serine/threonine~~-~~protein kinase involved in various processes such as neuronal proliferation, differentiation~~, ~~migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c~~-~~Jun N-terminal kinase (SAP/~~JNK~~) signaling pathway~~. ~~In this cascade~~, ~~two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn~~, ~~MAPK10/JNK3 phosphorylates a number of transcription factors~~, ~~primarily components of AP-~~1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-~~amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP~~. ~~Participates also in neurite growth in spiral ganglion neurons~~.<ref>PMID:~~11718727~~</ref>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[3tti]] 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=3TTI OCA].~~		</div>

	==~~Reference~~==		==See Also==
	~~<ref group~~=~~"xtra">PMID:022244937</ref>~~<references ~~group="xtra"~~/><~~references~~/>		*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
	[[Category: Albers, R.]]		[[Category: Albers, R]]
	[[Category: Ayala, L.]]		[[Category: Ayala, L]]
	[[Category: Bahmanyar, S.]]		[[Category: Bahmanyar, S]]
	[[Category: Bai, A.]]		[[Category: Bai, A]]
	[[Category: Benish, B.]]		[[Category: Benish, B]]
	[[Category: Bennett, B.]]		[[Category: Bennett, B]]
	[[Category: Blease, K.]]		[[Category: Blease, K]]
	[[Category: Bodine, T.]]		[[Category: Bodine, T]]
	[[Category: Cathers, B E.]]		[[Category: Cathers, B E]]
	[[Category: Celeridad, M.]]		[[Category: Celeridad, M]]
	[[Category: Chamberlain, P.]]		[[Category: Chamberlain, P]]
	[[Category: Clareen, S.]]		[[Category: Clareen, S]]
	[[Category: Delgado, M.]]		[[Category: Delgado, M]]
	[[Category: Delker, S L.]]		[[Category: Delker, S L]]
	[[Category: Fan, R.]]		[[Category: Fan, R]]
	[[Category: Giegel, D.]]		[[Category: Giegel, D]]
	[[Category: Hegde, S.]]		[[Category: Hegde, S]]
	[[Category: Hilgraf, R.]]		[[Category: Hilgraf, R]]
	[[Category: Katz, J.]]		[[Category: Katz, J]]
	[[Category: Khatsenko, O.]]		[[Category: Khatsenko, O]]
	[[Category: Lachowitzer, J.]]		[[Category: Lachowitzer, J]]
	[[Category: McCarrick, M.]]		[[Category: McCarrick, M]]
	[[Category: Moghaddam, M.]]		[[Category: Moghaddam, M]]
	[[Category: Muir, J.]]		[[Category: Muir, J]]
	[[Category: Nadolny, L.]]		[[Category: Nadolny, L]]
	[[Category: Plantevin-Krenitsky, V.]]		[[Category: Plantevin-Krenitsky, V]]
	[[Category: Raymon, H.]]		[[Category: Raymon, H]]
	[[Category: Sapienza, J.]]		[[Category: Sapienza, J]]
	[[Category: Satoh, Y.]]		[[Category: Satoh, Y]]
	[[Category: Shirley, M A.]]		[[Category: Shirley, M A]]
	[[Category: Sidocky, N D.]]		[[Category: Sidocky, N D]]
	[[Category: Tang, Y.]]		[[Category: Tang, Y]]
	[[Category: Wright, J.]]		[[Category: Wright, J]]
	[[Category: Xu, L.]]		[[Category: Xu, L]]
	[[Category: Jnk3]]		[[Category: Jnk3]]
	[[Category: Kinase]]		[[Category: Kinase]]

OCA at 10:12, 24 March 2013

2013-03-24T10:12:24Z

← Older revision		Revision as of 10:12, 24 March 2013
Line 1:		Line 1:
	~~[[Image:3tti.png\|left\|200px]]~~

	{{STRUCTURE_3tti\| PDB=3tti \| SCENE= }}		{{STRUCTURE_3tti\| PDB=3tti \| SCENE= }}
			===Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor===
			{{ABSTRACT_PUBMED_22244937}}

	===~~Crystal Structure~~ of ~~JNK3 complexed with CC~~-~~930, an orally active anti~~-~~fibrotic JNK inhibitor==~~=		==Disease==
			[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[http://omim.org/entry/606369 606369]]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.

	~~{{ABSTRACT_PUBMED_22244937}}~~		==Function==
			[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
	<ref group="xtra">PMID:022244937</ref><references group="xtra"/>		<ref group="xtra">PMID:022244937</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]

OCA at 10:28, 8 August 2012

2012-08-08T10:28:28Z

← Older revision		Revision as of 10:28, 8 August 2012
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	[[Image:3tti.png\|left\|200px]]		[[Image:3tti.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3tti", 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.~~
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	{{STRUCTURE_3tti\| PDB=3tti \| SCENE= }}		{{STRUCTURE_3tti\| PDB=3tti \| SCENE= }}

	===Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor===		===Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor===


	~~<!--~~
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	{{ABSTRACT_PUBMED_22244937}}		{{ABSTRACT_PUBMED_22244937}}

OCA at 05:50, 8 February 2012

2012-02-08T05:50:55Z

← Older revision		Revision as of 05:50, 8 February 2012
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	[[Image:3tti.~~jpg~~\|left\|200px]]		[[Image:3tti.png\|left\|200px]]

	<!--		<!--

OCA at 07:24, 1 February 2012

2012-02-01T07:24:10Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:3tti.jpg|left|200px]]
-The entry 3tti is ON HOLD
+<!--
-Authors: Plantevin-Krenitsky, V., Nadolny, L., Delgado, M., Ayala, L., Clareen, S., Hilgraf, R., Albers, R., Hegde, S., D'Sidocky, N., Sapienza, J., Wright, J., McCarrick, M., Bahmanyar, S., Chamberlain, P., Delker, S.L., Muir, J., Giegel, D., Xu, L., Celeridad, M., Lachowitzer, J., Bennett, B., Moghaddam, M., Khatsenko, O., Katz, J., Fan, R., Bai, A., Tang, Y., Shirley, M.A., Benish, B., Bodine, T., Blease, K., Raymon, H., Cathers, B.E., Satoh, Y.
+===Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor===
-Description: Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor

OCA at 08:43, 30 October 2011

2011-10-30T08:43:15Z

← Older revision		Revision as of 08:43, 30 October 2011
Line 3:		Line 3:
	The entry 3tti is ON HOLD		The entry 3tti is ON HOLD

	Authors: Plantevin Krenitsky, V, Nadolny, L, Delgado, M, Ayala, L, Clareen, S, Hilgraf, R, Albers, R, Hegde, S, D'Sidocky, N, Sapienza, J, Wright, J, McCarrick, M, Bahmanyar, S, Chamberlain, P, Delker, SL, Muir, J, Giegel, D, Xu, L, Celeridad, M, Lachowitzer, J, Bennett, B, Moghaddam, M, Khatsenko, O, Katz, J, Fan, R, Bai, A, Tang, Y, Shirley, MA, Benish, B, Bodine, T, Blease, K, Raymon, H, Cathers, BE, Satoh,Y		Authors: Plantevin-Krenitsky, V., Nadolny, L., Delgado, M., Ayala, L., Clareen, S., Hilgraf, R., Albers, R., Hegde, S., D'Sidocky, N., Sapienza, J., Wright, J., McCarrick, M., Bahmanyar, S., Chamberlain, P., Delker, S.L., Muir, J., Giegel, D., Xu, L., Celeridad, M., Lachowitzer, J., Bennett, B., Moghaddam, M., Khatsenko, O., Katz, J., Fan, R., Bai, A., Tang, Y., Shirley, M.A., Benish, B., Bodine, T., Blease, K., Raymon, H., Cathers, B.E., Satoh, Y.

	Description: Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor		Description: Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor