4qta - Revision history

OCA at 17:37, 20 September 2023

2023-09-20T17:37:57Z

←Older revision		Revision as of 17:37, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qta]] 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=4QTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QTA FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qta]] 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=4QTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QTA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.45Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [https://pdbe.org/4qta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [https://www.ebi.ac.uk/pdbsum/4qta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qta 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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [https://pdbe.org/4qta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [https://www.ebi.ac.uk/pdbsum/4qta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qta ProSAT]</span></td></tr>
	</table>		</table>

OCA at 13:51, 22 February 2023

2023-02-22T13:51:35Z

←Older revision		Revision as of 13:51, 22 February 2023
Line 3:		Line 3:
	<StructureSection load='4qta' size='340' side='right'caption='[[4qta]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='4qta' size='340' side='right'caption='[[4qta]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qta]] 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=4QTA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QTA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qta]] 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=4QTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QTA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qtb\|4qtb]], [[4qtc\|4qtc]], [[4qtd\|4qtd]], [[4qte\|4qte]]</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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [https://pdbe.org/4qta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [https://www.ebi.ac.uk/pdbsum/4qta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qta ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERK2, MAPK1, PRKM1, PRKM2 ([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='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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [~~http~~://pdbe.org/4qta PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qta PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qta ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MK01_HUMAN MK01_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint.<ref>PMID:7588608</ref> <ref>PMID:8622688</ref> <ref>PMID:9480836</ref> <ref>PMID:9687510</ref> <ref>PMID:9649500</ref> <ref>PMID:9596579</ref> <ref>PMID:10637505</ref> <ref>PMID:10617468</ref> <ref>PMID:11154262</ref> <ref>PMID:12110590</ref> <ref>PMID:12356731</ref> <ref>PMID:12974390</ref> <ref>PMID:12794087</ref> <ref>PMID:12792650</ref> <ref>PMID:15184391</ref> <ref>PMID:15241487</ref> <ref>PMID:15952796</ref> <ref>PMID:15616583</ref> <ref>PMID:15788397</ref> <ref>PMID:15664191</ref> <ref>PMID:16581800</ref> <ref>PMID:19879846</ref> <ref>PMID:19265199</ref> Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.<ref>PMID:7588608</ref> <ref>PMID:8622688</ref> <ref>PMID:9480836</ref> <ref>PMID:9687510</ref> <ref>PMID:9649500</ref> <ref>PMID:9596579</ref> <ref>PMID:10637505</ref> <ref>PMID:10617468</ref> <ref>PMID:11154262</ref> <ref>PMID:12110590</ref> <ref>PMID:12356731</ref> <ref>PMID:12974390</ref> <ref>PMID:12794087</ref> <ref>PMID:12792650</ref> <ref>PMID:15184391</ref> <ref>PMID:15241487</ref> <ref>PMID:15952796</ref> <ref>PMID:15616583</ref> <ref>PMID:15788397</ref> <ref>PMID:15664191</ref> <ref>PMID:16581800</ref> <ref>PMID:19879846</ref> <ref>PMID:19265199</ref>	+	[https://www.uniprot.org/uniprot/MK01_HUMAN MK01_HUMAN] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint.<ref>PMID:7588608</ref> <ref>PMID:8622688</ref> <ref>PMID:9480836</ref> <ref>PMID:9687510</ref> <ref>PMID:9649500</ref> <ref>PMID:9596579</ref> <ref>PMID:10637505</ref> <ref>PMID:10617468</ref> <ref>PMID:11154262</ref> <ref>PMID:12110590</ref> <ref>PMID:12356731</ref> <ref>PMID:12974390</ref> <ref>PMID:12794087</ref> <ref>PMID:12792650</ref> <ref>PMID:15184391</ref> <ref>PMID:15241487</ref> <ref>PMID:15952796</ref> <ref>PMID:15616583</ref> <ref>PMID:15788397</ref> <ref>PMID:15664191</ref> <ref>PMID:16581800</ref> <ref>PMID:19879846</ref> <ref>PMID:19265199</ref> Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.<ref>PMID:7588608</ref> <ref>PMID:8622688</ref> <ref>PMID:9480836</ref> <ref>PMID:9687510</ref> <ref>PMID:9649500</ref> <ref>PMID:9596579</ref> <ref>PMID:10637505</ref> <ref>PMID:10617468</ref> <ref>PMID:11154262</ref> <ref>PMID:12110590</ref> <ref>PMID:12356731</ref> <ref>PMID:12974390</ref> <ref>PMID:12794087</ref> <ref>PMID:12792650</ref> <ref>PMID:15184391</ref> <ref>PMID:15241487</ref> <ref>PMID:15952796</ref> <ref>PMID:15616583</ref> <ref>PMID:15788397</ref> <ref>PMID:15664191</ref> <ref>PMID:16581800</ref> <ref>PMID:19879846</ref> <ref>PMID:19265199</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]	+	*[[Mitogen-activated protein kinase 3D structures\|Mitogen-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Mitogen-activated protein kinase]]~~	+	[[Category: Arrowsmith CH]]
-	[[Category: Arrowsmith~~, C H~~]]	+	[[Category: Bountra C]]
-	[[Category: Bountra, C]]	+	[[Category: Chaikuad A]]
-	[[Category: Chaikuad, A]]	+	[[Category: Edwards AM]]
-	~~[[Category: Delft, F von~~]]	+	[[Category: Knapp S]]
-	[[Category: Edwards~~, A M~~]]	+	[[Category: Savitsky P]]
-	[[Category: Knapp, S]]	+	[[Category: Von Delft F]]
-	~~[[Category: Structural genomic~~]]	+
-	[[Category: Savitsky, P]]	+
-	[[Category: ~~Allosteric]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Mapk]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Signalling]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 09:35, 24 April 2019

2019-04-24T09:35:30Z

←Older revision		Revision as of 09:35, 24 April 2019
Line 1:		Line 1:

	==Structure of human ERK2 in complex with SCH772984 revealing a novel inhibitor-induced binding pocket==		==Structure of human ERK2 in complex with SCH772984 revealing a novel inhibitor-induced binding pocket==
-	<StructureSection load='4qta' size='340' side='right' caption='[[4qta]], [[Resolution\|resolution]] 1.45Å' scene=''>	+	<StructureSection load='4qta' size='340' side='right'caption='[[4qta]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qta]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QTA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QTA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qta]] 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=4QTA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QTA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qtb\|4qtb]], [[4qtc\|4qtc]], [[4qtd\|4qtd]], [[4qte\|4qte]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qtb\|4qtb]], [[4qtc\|4qtc]], [[4qtd\|4qtd]], [[4qte\|4qte]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERK2, MAPK1, PRKM1, PRKM2 ([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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://pdbe.org/4qta PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qta ProSAT]</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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://pdbe.org/4qta PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qta ProSAT]</span></td></tr>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4qta" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4qta" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]

OCA at 10:44, 4 August 2016

2016-08-04T10:44:11Z

←Older revision		Revision as of 10:44, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of human ERK2 in complex with SCH772984 revealing a novel inhibitor-induced binding pocket==		==Structure of human ERK2 in complex with SCH772984 revealing a novel inhibitor-induced binding pocket==
	<StructureSection load='4qta' size='340' side='right' caption='[[4qta]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='4qta' size='340' side='right' caption='[[4qta]], [[Resolution\|resolution]] 1.45Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qtb\|4qtb]], [[4qtc\|4qtc]], [[4qtd\|4qtd]], [[4qte\|4qte]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qtb\|4qtb]], [[4qtc\|4qtc]], [[4qtd\|4qtd]], [[4qte\|4qte]]</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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta 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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://pdbe.org/4qta PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qta ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4qta" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:29, 25 December 2014

2014-12-25T08:29:00Z

←Older revision		Revision as of 08:29, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qta]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QTA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QTA FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qta]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QTA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QTA FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qtb\|4qtb]], [[4qtc\|4qtc]], [[4qtd\|4qtd]], [[4qte\|4qte]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qtb\|4qtb]], [[4qtc\|4qtc]], [[4qtd\|4qtd]], [[4qte\|4qte]]</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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta 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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MK01_HUMAN MK01_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint.<ref>PMID:7588608</ref> <ref>PMID:8622688</ref> <ref>PMID:9480836</ref> <ref>PMID:9687510</ref> <ref>PMID:9649500</ref> <ref>PMID:9596579</ref> <ref>PMID:10637505</ref> <ref>PMID:10617468</ref> <ref>PMID:11154262</ref> <ref>PMID:12110590</ref> <ref>PMID:12356731</ref> <ref>PMID:12974390</ref> <ref>PMID:12794087</ref> <ref>PMID:12792650</ref> <ref>PMID:15184391</ref> <ref>PMID:15241487</ref> <ref>PMID:15952796</ref> <ref>PMID:15616583</ref> <ref>PMID:15788397</ref> <ref>PMID:15664191</ref> <ref>PMID:16581800</ref> <ref>PMID:19879846</ref> <ref>PMID:19265199</ref> Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.<ref>PMID:7588608</ref> <ref>PMID:8622688</ref> <ref>PMID:9480836</ref> <ref>PMID:9687510</ref> <ref>PMID:9649500</ref> <ref>PMID:9596579</ref> <ref>PMID:10637505</ref> <ref>PMID:10617468</ref> <ref>PMID:11154262</ref> <ref>PMID:12110590</ref> <ref>PMID:12356731</ref> <ref>PMID:12974390</ref> <ref>PMID:12794087</ref> <ref>PMID:12792650</ref> <ref>PMID:15184391</ref> <ref>PMID:15241487</ref> <ref>PMID:15952796</ref> <ref>PMID:15616583</ref> <ref>PMID:15788397</ref> <ref>PMID:15664191</ref> <ref>PMID:16581800</ref> <ref>PMID:19879846</ref> <ref>PMID:19265199</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
-	[[Category: Arrowsmith, C H.]]	+	[[Category: Arrowsmith, C H]]
-	[[Category: Bountra, C.]]	+	[[Category: Bountra, C]]
-	[[Category: Chaikuad, A.]]	+	[[Category: Chaikuad, A]]
-	[[Category: Delft, F von.]]	+	[[Category: Delft, F von]]
-	[[Category: Edwards, A M.]]	+	[[Category: Edwards, A M]]
-	[[Category: Knapp, S.]]	+	[[Category: Knapp, S]]
-	[[Category: ~~SGC,~~ Structural ~~Genomics Consortium.~~]]	+	[[Category: Structural genomic]]
-	[[Category: Savitsky, P.]]	+	[[Category: Savitsky, P]]
	[[Category: Allosteric]]		[[Category: Allosteric]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
Line 35:		Line 37:
	[[Category: Sgc]]		[[Category: Sgc]]
	[[Category: Signalling]]		[[Category: Signalling]]
-	[[Category: Structural genomic]]
-	[[Category: Structural genomics consortium]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:06, 24 September 2014

2014-09-24T07:06:16Z

←Older revision		Revision as of 07:06, 24 September 2014
Line 8:		Line 8:
	<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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta PDBsum]</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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta PDBsum]</span></td></tr>
	<table>		<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Activation of the ERK pathway is a hallmark of cancer, and targeting of upstream signaling partners led to the development of approved drugs. Recently, SCH772984 has been shown to be a selective and potent ERK1/2 inhibitor. Here we report the structural mechanism for its remarkable selectivity. In ERK1/2, SCH772984 induces a so-far-unknown binding pocket that accommodates the piperazine-phenyl-pyrimidine decoration. This new binding pocket was created by an inactive conformation of the phosphate-binding loop and an outward tilt of helix alphaC. In contrast, structure determination of SCH772984 with the off-target haspin and JNK1 revealed two canonical but distinct type I binding modes. Notably, the new binding mode with ERK1/2 was associated with slow binding kinetics in vitro as well as in cell-based assay systems. The described binding mode of SCH772984 with ERK1/2 enables the design of a new type of specific kinase inhibitors with prolonged on-target activity.
		+
		+	A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics.,Chaikuad A, M C Tacconi E, Zimmer J, Liang Y, Gray NS, Tarsounas M, Knapp S Nat Chem Biol. 2014 Oct;10(10):853-60. doi: 10.1038/nchembio.1629. Epub 2014 Sep , 7. PMID:25195011<ref>PMID:25195011</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:14, 23 July 2014

2014-07-23T08:14:24Z

←Older revision		Revision as of 08:14, 23 July 2014
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Structure of human ERK2 in complex with SCH772984 revealing a novel inhibitor-induced binding pocket==
-		+	<StructureSection load='4qta' size='340' side='right' caption='[[4qta]], [[Resolution\|resolution]] 1.45Å' scene=''>
-	~~The entry~~ 4qta is ~~ON HOLD~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4qta]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QTA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QTA FirstGlance]. <br>
-	~~Authors~~: ~~Chaikuad~~, A., ~~Savitsky~~, P., ~~von Delft~~, F., Arrowsmith, C.H., ~~Edwards~~, A.M., ~~Bountra, C~~., Knapp, S., Structural Genomics Consortium ~~(SGC)~~	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38Z:(3R)-1-(2-OXO-2-{4-[4-(PYRIMIDIN-2-YL)PHENYL]PIPERAZIN-1-YL}ETHYL)-N-[3-(PYRIDIN-4-YL)-2H-INDAZOL-5-YL]PYRROLIDINE-3-CARBOXAMIDE'>38Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
-		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4qtb\|4qtb]], [[4qtc\|4qtc]], [[4qtd\|4qtd]], [[4qte\|4qte]]</td></tr>
-	~~Description~~: ~~Structure of human ERK2 in complex with SCH772984 revealing a novel inhibitor~~-~~induced binding pocket~~	+	<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=4qta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qta OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qta RCSB], [http://www.ebi.ac.uk/pdbsum/4qta PDBsum]</span></td></tr>
		+	<table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase]]
		+	[[Category: Arrowsmith, C H.]]
		+	[[Category: Bountra, C.]]
		+	[[Category: Chaikuad, A.]]
		+	[[Category: Delft, F von.]]
		+	[[Category: Edwards, A M.]]
		+	[[Category: Knapp, S.]]
		+	[[Category: SGC, Structural Genomics Consortium.]]
		+	[[Category: Savitsky, P.]]
		+	[[Category: Allosteric]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Mapk]]
		+	[[Category: Sgc]]
		+	[[Category: Signalling]]
		+	[[Category: Structural genomic]]
		+	[[Category: Structural genomics consortium]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

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

2014-07-16T09:48:47Z

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

←Older revision

Revision as of 09:48, 16 July 2014

OCA: New page: '''Unreleased structure''' The entry 4qta is ON HOLD Authors: Chaikuad, A., Savitsky, P., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Knapp, S., Structural Genomics Con...

2014-07-16T09:48:46Z

New page: '''Unreleased structure''' The entry 4qta is ON HOLD Authors: Chaikuad, A., Savitsky, P., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Knapp, S., Structural Genomics Con...

New page

'''Unreleased structure'''

The entry 4qta is ON HOLD

Authors: Chaikuad, A., Savitsky, P., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Knapp, S., Structural Genomics Consortium (SGC)

Description: Structure of human ERK2 in complex with SCH772984 revealing a novel inhibitor-induced binding pocket