1pmq - Revision history

OCA: Redirecting to 4z9l

2015-05-06T12:34:11Z

Redirecting to 4z9l

←Older revision		Revision as of 12:34, 6 May 2015
Line 1:		Line 1:
-	~~==The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor==~~	+	#REDIRECT [[4z9l]] This PDB entry is obsolete and replaced by 4z9l
-	~~<StructureSection load='1pmq' size='340' side='right' caption='~~[[~~1pmq]], [[Resolution\|resolution]] 2.20Å' scene=''>~~	+
-	~~== Structural highlights ==~~	+
-	~~<table><tr><td colspan='2'>[[1pmq~~]] 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=1PMQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PMQ FirstGlance]. <br>	+
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=880:CYCLOHEXYL-{4-[5-(3,4-DICHLOROPHENYL)-2-PIPERIDIN-4-YL-3-PROPYL-3H-IMIDAZOL-4-YL]-PYRIMIDIN-2-YL}AMINE'>880</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>	+
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pmn\|1pmn]], [[1pmu\|1pmu]], [[1pmv\|1pmv]]</td></tr>~~	+
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MK10_HUMAN ([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=1pmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pmq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1pmq RCSB], [http://www.ebi.ac.uk/pdbsum/1pmq 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.~~	+
-	~~== 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>~~	+
-	~~== Evolutionary Conservation ==~~	+
-	~~[[Image:Consurf_key_small.gif\|200px\|right]]~~	+
-	~~Check<jmol>~~	+
-	~~<jmolCheckbox>~~	+
-	~~<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pm/1pmq_consurf.spt"</scriptWhenChecked>~~	+
-	~~<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>~~	+
-	~~<text>to colour the structure by Evolutionary Conservation</text>~~	+
-	~~</jmolCheckbox>~~	+
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].	+
-	~~<div style="clear:both"></div>~~	+
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The c-Jun terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and as such, JNK3 may represent an attractive target for the treatment of neurological disorders. The MAP kinases share between 50% and 80% sequence identity. In order to obtain efficacious and safe compounds, it is necessary to address the issues of potency and selectivity. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity.	+
-		+
-	The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity.,Scapin G, Patel SB, Lisnock J, Becker JW, LoGrasso PV Chem Biol. 2003 Aug;10(8):705-12. PMID:12954329<ref>PMID:12954329</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-		+
-	~~==See Also==~~	+
-	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]	+
-	~~== References ==~~	+
-	~~<references/>~~	+
-	~~__TOC__~~	+
-	~~</StructureSection>~~	+
-	~~[[Category: Homo sapiens]]~~	+
-	~~[[Category: Mitogen-activated protein kinase]]~~	+
-	~~[[Category: Becker, J W]]~~	+
-	~~[[Category: Lisnock, J]]~~	+
-	~~[[Category: LoGrasso, P V]]~~	+
-	~~[[Category: Patel, S B]]~~	+
-	~~[[Category: Scapin, G]]~~	+
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Inhibition]]~~	+
-	~~[[Category: Map kinase]]~~	+
-	~~[[Category: Transferase]]~~	+

OCA at 07:44, 6 January 2015

2015-01-06T07:44:45Z

←Older revision		Revision as of 07:44, 6 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1pmq]] 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=1PMQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PMQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[1pmq]] 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=1PMQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PMQ FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=880:CYCLOHEXYL-{4-[5-(3,4-DICHLOROPHENYL)-2-PIPERIDIN-4-YL-3-PROPYL-3H-IMIDAZOL-4-YL]-PYRIMIDIN-2-YL}AMINE'>880</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=880:CYCLOHEXYL-{4-[5-(3,4-DICHLOROPHENYL)-2-PIPERIDIN-4-YL-3-PROPYL-3H-IMIDAZOL-4-YL]-PYRIMIDIN-2-YL}AMINE'>880</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pmn\|1pmn]], [[1pmu\|1pmu]], [[1pmv\|1pmv]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pmn\|1pmn]], [[1pmu\|1pmu]], [[1pmv\|1pmv]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MK10_HUMAN ([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">MK10_HUMAN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pmq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1pmq RCSB], [http://www.ebi.ac.uk/pdbsum/1pmq 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=1pmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pmq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1pmq RCSB], [http://www.ebi.ac.uk/pdbsum/1pmq PDBsum]</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.		[[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.
Line 40:		Line 40:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
-	[[Category: Becker, J W.]]	+	[[Category: Becker, J W]]
-	[[Category: Lisnock, J.]]	+	[[Category: Lisnock, J]]
-	[[Category: LoGrasso, P V.]]	+	[[Category: LoGrasso, P V]]
-	[[Category: Patel, S B.]]	+	[[Category: Patel, S B]]
-	[[Category: Scapin, G.]]	+	[[Category: Scapin, G]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Inhibition]]		[[Category: Inhibition]]
	[[Category: Map kinase]]		[[Category: Map kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 16:20, 29 September 2014

2014-09-29T16:20:22Z

←Older revision		Revision as of 16:20, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1pmq\| PDB=1pmq \| SCENE= }}~~	+	==The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor==
-	===The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor===	+	<StructureSection load='1pmq' size='340' side='right' caption='[[1pmq]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	{~~{ABSTRACT_PUBMED_12954329}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[1pmq]] 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=1PMQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PMQ FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=880:CYCLOHEXYL-{4-[5-(3,4-DICHLOROPHENYL)-2-PIPERIDIN-4-YL-3-PROPYL-3H-IMIDAZOL-4-YL]-PYRIMIDIN-2-YL}AMINE'>880</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pmn\|1pmn]], [[1pmu\|1pmu]], [[1pmv\|1pmv]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MK10_HUMAN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pmq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1pmq RCSB], [http://www.ebi.ac.uk/pdbsum/1pmq 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>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pm/1pmq_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The c-Jun terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and as such, JNK3 may represent an attractive target for the treatment of neurological disorders. The MAP kinases share between 50% and 80% sequence identity. In order to obtain efficacious and safe compounds, it is necessary to address the issues of potency and selectivity. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity.

-	~~==Function==~~	+	The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity.,Scapin G, Patel SB, Lisnock J, Becker JW, LoGrasso PV Chem Biol. 2003 Aug;10(8):705-12. PMID:12954329<ref>PMID:12954329</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>
-	~~[[1pmq]] 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=1PMQ OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]		*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:012954329</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]

OCA at 19:26, 24 March 2013

2013-03-24T19:26:41Z

←Older revision		Revision as of 19:26, 24 March 2013
Line 1:		Line 1:
-	[[Image:1pmq.png\|left\|200px]]
-
	{{STRUCTURE_1pmq\| PDB=1pmq \| SCENE= }}		{{STRUCTURE_1pmq\| PDB=1pmq \| SCENE= }}
-
	===The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor===		===The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor===
		+	{{ABSTRACT_PUBMED_12954329}}

-	~~{{ABSTRACT_PUBMED_12954329}}~~	+	==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.
		+
		+	==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 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:012954329</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012954329</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]

OCA at 15:14, 20 October 2012

2012-10-20T15:14:43Z

←Older revision		Revision as of 15:14, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1pmq]] is a 1 chain structure ~~of [[Mitogen-activated protein kinase]]~~ 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=1PMQ OCA].	+	[[1pmq]] 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=1PMQ OCA].

	==See Also==		==See Also==

OCA: Protected "1pmq" [edit=sysop:move=sysop]

2012-07-26T17:45:08Z

Protected "1pmq" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:45, 26 July 2012

OCA at 17:45, 26 July 2012

2012-07-26T17:45:05Z

←Older revision		Revision as of 17:45, 26 July 2012
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-	{{Seed}}
	[[Image:1pmq.png\|left\|200px]]		[[Image:1pmq.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1pmq", 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_1pmq\| PDB=1pmq \| SCENE= }}		{{STRUCTURE_1pmq\| PDB=1pmq \| SCENE= }}

	===The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor===		===The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_12954329}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 12954329 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_12954329}}		{{ABSTRACT_PUBMED_12954329}}

	==About this Structure==		==About this Structure==
-	~~1PMQ~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PMQ OCA].	+	[[1pmq]] is a 1 chain structure of [[Mitogen-activated protein kinase]] 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=1PMQ OCA].
		+
		+	==See Also==
		+	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~12954329~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012954329</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
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	[[Category: Inhibition]]		[[Category: Inhibition]]
	[[Category: Map kinase]]		[[Category: Map kinase]]
-		+	[[Category: Transferase]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Tue Feb 17 12:58:55 2009''~~	+

OCA at 10:58, 17 February 2009

2009-02-17T10:58:56Z

←Older revision		Revision as of 10:58, 17 February 2009
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	==About this Structure==		==About this Structure==
-	1PMQ is a ~~[[Single protein]]~~ structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PMQ OCA].	+	1PMQ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PMQ OCA].

	==Reference==		==Reference==
-	~~The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity., Scapin G, Patel SB, Lisnock J, Becker JW, LoGrasso PV, Chem Biol. 2003 Aug;10(8):705-12.~~ PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/12954329 12954329]~~	+	<ref group="xtra">PMID:12954329</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
-	[[Category: Single protein]]
	[[Category: Becker, J W.]]		[[Category: Becker, J W.]]
	[[Category: Lisnock, J.]]		[[Category: Lisnock, J.]]
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	[[Category: Map kinase]]		[[Category: Map kinase]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Mon Jul 28~~ 17:26:~~57 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 12:58:55 2009''

OCA at 14:26, 28 July 2008

2008-07-28T14:26:58Z

←Older revision		Revision as of 14:26, 28 July 2008
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-	[[Image:1pmq.~~gif~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:1pmq.png\|left\|200px]]

	<!--		<!--
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	{{STRUCTURE_1pmq\| PDB=1pmq \| SCENE= }}		{{STRUCTURE_1pmq\| PDB=1pmq \| SCENE= }}

-	~~'''~~The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor~~'''~~	+	===The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor===


-	~~==Overview==~~	+	<!--
-	The ~~c-Jun terminal kinases (JNKs) are members of~~ the ~~mitogen-activated protein~~ (~~MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and~~ as ~~such, JNK3 may represent an attractive target for the treatment of neurological disorders~~. ~~The MAP kinases share between 50% and 80% sequence identity~~. ~~In order to obtain efficacious and safe compounds~~, it is ~~necessary to address~~ the ~~issues of potency and selectivity~~. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-~~guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity.~~	+	The line below this paragraph, {{ABSTRACT_PUBMED_12954329}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 12954329 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_12954329}}

	==About this Structure==		==About this Structure==
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	[[Category: Inhibition]]		[[Category: Inhibition]]
	[[Category: Map kinase]]		[[Category: Map kinase]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sat May 3 05~~:15:21 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:26:57 2008''

OCA at 02:15, 3 May 2008

2008-05-03T02:15:23Z

←Older revision		Revision as of 02:15, 3 May 2008
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	[[Image:1pmq.gif\|left\|200px]]		[[Image:1pmq.gif\|left\|200px]]

-	~~{{Structure~~	+	<!--
-	~~\|PDB= 1pmq \|SIZE=350\|CAPTION= <scene name='initialview01'>1pmq</scene>~~, ~~resolution 2~~.~~2Å~~	+	The line below this paragraph, containing "STRUCTURE_1pmq", creates the "Structure Box" on the page.
-	~~\|SITE=~~	+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	~~\|LIGAND= <~~scene ~~name='pdbligand=880:CYCLOHEXYL-{4-[5-(3,4-DICHLOROPHENYL~~)~~-2-PIPERIDIN-4-YL-3-PROPYL-3H-IMIDAZOL-4-YL]-PYRIMIDIN-2-YL}AMINE'>880</scene>~~, ~~<scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>~~	+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	~~\|ACTIVITY= <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~~>	+	or leave the SCENE parameter empty for the default display.
-	\|~~GENE~~= ~~MK10_HUMAN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])~~	+	-->
-	\|~~DOMAIN~~=	+	{{STRUCTURE_1pmq\| PDB=1pmq \| SCENE= }}
-	~~\|RELATEDENTRY=[[1pmn\|1PMN]], [[1pmu\|1PMU]], [[1pmv\|1PMV]]~~	+
-	\|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pmq OCA], [http://www.ebi.ac.uk/pdbsum/1pmq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pmq RCSB]</span>	+
-	}}	+

	'''The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor'''		'''The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor'''
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	[[Category: Patel, S B.]]		[[Category: Patel, S B.]]
	[[Category: Scapin, G.]]		[[Category: Scapin, G.]]
-	[[Category: ~~apoptosis~~]]	+	[[Category: Apoptosis]]
-	[[Category: ~~inhibition~~]]	+	[[Category: Inhibition]]
-	[[Category: ~~map~~ kinase]]	+	[[Category: Map kinase]]
-		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:15:21 2008''
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun Mar 30 23~~:01:42 2008''	+