4mao - Revision history

OCA at 11:06, 21 December 2022

OCA — Wed, 21 Dec 2022 11:06:42 GMT

←Older revision		Revision as of 11:06, 21 December 2022
Line 3:		Line 3:
	<StructureSection load='4mao' size='340' side='right'caption='[[4mao]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4mao' size='340' side='right'caption='[[4mao]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4mao]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MAO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4MAO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4mao]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MAO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=28D:(2Z)-2-(1H-1,2,4-TRIAZOL-1-YL)-3-[3-(3,4,5-TRIMETHOXYPHENYL)-1H-INDAZOL-5-YL]PROP-2-ENENITRILE'>28D</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=28D:(2Z)-2-(1H-1,2,4-TRIAZOL-1-YL)-3-[3-(3,4,5-TRIMETHOXYPHENYL)-1H-INDAZOL-5-YL]PROP-2-ENENITRILE'>28D</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4m8t\|4m8t]]</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=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [https://pdbe.org/4mao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [https://www.ebi.ac.uk/pdbsum/4mao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mao ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Rps6ka3, Mapkapk1b, Rps6ka-rs1, Rsk2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [~~http~~://pdbe.org/4mao PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4mao PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4mao ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KS6A3_MOUSE KS6A3_MOUSE]] Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1 (By similarity).<ref>PMID:10856237</ref> <ref>PMID:14504289</ref> <ref>PMID:17785202</ref> <ref>PMID:17906627</ref>	+	[https://www.uniprot.org/uniprot/KS6A3_MOUSE KS6A3_MOUSE] Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1 (By similarity).<ref>PMID:10856237</ref> <ref>PMID:14504289</ref> <ref>PMID:17785202</ref> <ref>PMID:17906627</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice]]~~	+	[[Category: Mus musculus]]
-	~~[[Category: Non-specific serine/threonine protein kinase~~]]	+	[[Category: Miller RM]]
-	[[Category: Miller~~, R M~~]]	+	[[Category: Taunton J]]
-	[[Category: Taunton, J]]	+
-	~~[[Category: Covalent inhibitor]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 09:02, 3 April 2019

OCA — Wed, 03 Apr 2019 09:02:20 GMT

←Older revision		Revision as of 09:02, 3 April 2019
Line 1:		Line 1:

	==RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58==		==RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58==
-	<StructureSection load='4mao' size='340' side='right' caption='[[4mao]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='4mao' size='340' side='right'caption='[[4mao]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4mao]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MAO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MAO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4mao]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MAO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MAO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=28D:(2Z)-2-(1H-1,2,4-TRIAZOL-1-YL)-3-[3-(3,4,5-TRIMETHOXYPHENYL)-1H-INDAZOL-5-YL]PROP-2-ENENITRILE'>28D</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=28D:(2Z)-2-(1H-1,2,4-TRIAZOL-1-YL)-3-[3-(3,4,5-TRIMETHOXYPHENYL)-1H-INDAZOL-5-YL]PROP-2-ENENITRILE'>28D</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4m8t\|4m8t]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4m8t\|4m8t]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Rps6ka3, Mapkapk1b, Rps6ka-rs1, Rsk2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [http://pdbe.org/4mao PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [http://www.ebi.ac.uk/pdbsum/4mao PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mao 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=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [http://pdbe.org/4mao PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [http://www.ebi.ac.uk/pdbsum/4mao PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mao ProSAT]</span></td></tr>
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Miller, R M]]		[[Category: Miller, R M]]

OCA at 11:00, 5 August 2016

OCA — Fri, 05 Aug 2016 11:00:23 GMT

←Older revision		Revision as of 11:00, 5 August 2016
Line 1:		Line 1:
		+
	==RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58==		==RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58==
	<StructureSection load='4mao' size='340' side='right' caption='[[4mao]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4mao' size='340' side='right' caption='[[4mao]], [[Resolution\|resolution]] 2.60Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4m8t\|4m8t]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4m8t\|4m8t]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [http://www.ebi.ac.uk/pdbsum/4mao 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=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [http://pdbe.org/4mao PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [http://www.ebi.ac.uk/pdbsum/4mao PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mao 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 4mao" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ribosomal protein S6 kinase\|Ribosomal protein S6 kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:15, 25 December 2014

OCA — Thu, 25 Dec 2014 18:15:08 GMT

←Older revision		Revision as of 18:15, 25 December 2014
Line 8:		Line 8:
	<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=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [http://www.ebi.ac.uk/pdbsum/4mao 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=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [http://www.ebi.ac.uk/pdbsum/4mao PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KS6A3_MOUSE KS6A3_MOUSE]] Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1 (By similarity).<ref>PMID:10856237</ref> <ref>PMID:14504289</ref> <ref>PMID:17785202</ref> <ref>PMID:17906627</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: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Miller, R M.]]	+	[[Category: Miller, R M]]
-	[[Category: Taunton, J.]]	+	[[Category: Taunton, J]]
	[[Category: Covalent inhibitor]]		[[Category: Covalent inhibitor]]
	[[Category: Phosphorylation]]		[[Category: Phosphorylation]]
	[[Category: Protein kinase]]		[[Category: Protein kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 11:37, 22 October 2014

OCA — Wed, 22 Oct 2014 11:37:35 GMT

←Older revision		Revision as of 11:37, 22 October 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58==
		+	<StructureSection load='4mao' size='340' side='right' caption='[[4mao]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4mao]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MAO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MAO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=28D:(2Z)-2-(1H-1,2,4-TRIAZOL-1-YL)-3-[3-(3,4,5-TRIMETHOXYPHENYL)-1H-INDAZOL-5-YL]PROP-2-ENENITRILE'>28D</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4m8t\|4m8t]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mao OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mao RCSB], [http://www.ebi.ac.uk/pdbsum/4mao PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Electrophilic probes that covalently modify a cysteine thiol often show enhanced pharmacological potency and selectivity. Although reversible Michael acceptors have been reported, the structural requirements for reversibility are poorly understood. Here, we report a novel class of acrylonitrile-based Michael acceptors, activated by aryl or heteroaryl electron-withdrawing groups. We demonstrate that thiol adducts of these acrylonitriles undergo beta-elimination at rates that span more than 3 orders of magnitude. These rates correlate inversely with the computed proton affinity of the corresponding carbanions, enabling the intrinsic reversibility of the thiol-Michael reaction to be tuned in a predictable manner. We apply these principles to the design of new reversible covalent kinase inhibitors with improved properties. A cocrystal structure of one such inhibitor reveals specific noncovalent interactions between the 1,2,4-triazole activating group and the kinase. Our experimental and computational study enables the design of new Michael acceptors, expanding the palette of reversible, cysteine-targeted electrophiles.

-	~~The entry 4mao is ON HOLD until Jan 15 2016~~	+	Design of reversible, cysteine-targeted Michael acceptors guided by kinetic and computational analysis.,Krishnan S, Miller RM, Tian B, Mullins RD, Jacobson MP, Taunton J J Am Chem Soc. 2014 Sep 10;136(36):12624-30. doi: 10.1021/ja505194w. Epub 2014, Sep 2. PMID:25153195<ref>PMID:25153195</ref>

-	~~Authors~~: Miller, R.M., Taunton, J.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~RSK2 T493M C~~-~~Terminal Kinase Domain in Complex with RMM58~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Miller, R M.]]
		+	[[Category: Taunton, J.]]
		+	[[Category: Covalent inhibitor]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:48, 30 July 2014

OCA — Wed, 30 Jul 2014 06:48:19 GMT

←Older revision		Revision as of 06:48, 30 July 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4mao is ON HOLD until ~~Paper Publication~~	+	The entry 4mao is ON HOLD until Jan 15 2016

	Authors: Miller, R.M., Taunton, J.		Authors: Miller, R.M., Taunton, J.

	Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58		Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58

OCA at 06:55, 6 November 2013

OCA — Wed, 06 Nov 2013 06:55:14 GMT

←Older revision		Revision as of 06:55, 6 November 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4mao is ON HOLD	+	The entry 4mao is ON HOLD until Paper Publication

	Authors: Miller, R.M., Taunton, J.		Authors: Miller, R.M., Taunton, J.

	Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58		Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58

OCA at 03:36, 20 September 2013

OCA — Fri, 20 Sep 2013 03:36:37 GMT

←Older revision		Revision as of 03:36, 20 September 2013
Line 3:		Line 3:
	The entry 4mao is ON HOLD		The entry 4mao is ON HOLD

-	Authors: Miller, R. M., Taunton, J.	+	Authors: Miller, R.M., Taunton, J.

	Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58		Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58

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

OCA — Wed, 28 Aug 2013 06:55:18 GMT

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

←Older revision

Revision as of 06:55, 28 August 2013

OCA: New page: '''Unreleased structure''' The entry 4mao is ON HOLD Authors: Miller, R. M., Taunton, J. Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58

OCA — Wed, 28 Aug 2013 06:55:17 GMT

New page: '''Unreleased structure''' The entry 4mao is ON HOLD Authors: Miller, R. M., Taunton, J. Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58

New page

'''Unreleased structure'''

The entry 4mao is ON HOLD

Authors: Miller, R. M., Taunton, J.

Description: RSK2 T493M C-Terminal Kinase Domain in Complex with RMM58