3ubd - Revision history

OCA at 13:53, 14 March 2024

2024-03-14T13:53:30Z

←Older revision		Revision as of 13:53, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3ubd' size='340' side='right'caption='[[3ubd]], [[Resolution\|resolution]] 1.53Å' scene=''>		<StructureSection load='3ubd' size='340' side='right'caption='[[3ubd]], [[Resolution\|resolution]] 1.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ubd]] is a 1 chain structure with sequence from [https://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=3UBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UBD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ubd]] 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=3UBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UBD FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=SL0:5,7~~-~~DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3~~,~~4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</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]] 1.53Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>Mapkapk1b, Rps6ka-rs1, Rps6ka3, Rsk2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=10090 LK3 transgenic mice])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SL0:5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3,4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</scene></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Non~~-~~specific_serine/threonine_protein_kinase Non~~-~~specific serine/threonine protein kinase]~~, ~~with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [https://pdbe.org/3ubd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [https://www.ebi.ac.uk/pdbsum/3ubd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubd 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=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [https://pdbe.org/3ubd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [https://www.ebi.ac.uk/pdbsum/3ubd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[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>	+	[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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The p90 ribosomal S6 family of kinases (RSK) are potential drug targets, due to their involvement in cancer and other pathologies. There are currently only two known selective inhibitors of RSK, but the basis for selectivity is not known. One of these inhibitors is a naturally occurring kaempferol-alpha-l-diacetylrhamnoside, SL0101. Here, we report the crystal structure of the complex of the N-terminal kinase domain of the RSK2 isoform with SL0101 at 1.5 A resolution. The refined atomic model reveals unprecedented structural reorganization of the protein moiety, as compared to the nucleotide-bound form. The entire N-lobe, the hinge region, and the alphaD-helix undergo dramatic conformational changes resulting in a rearrangement of the nucleotide binding site with concomitant formation of a highly hydrophobic pocket spatially suited to accommodate SL0101. These unexpected results will be invaluable in further optimization of the SL0101 scaffold as a promising lead for a novel class of kinase inhibitors.	+
-		+
-	Insights into the Inhibition of the p90 Ribosomal S6 Kinase (RSK) by the Flavonol Glycoside SL0101 from the 1.5 A Crystal Structure of the N-Terminal Domain of RSK2 with Bound Inhibitor.,Utepbergenov D, Derewenda U, Olekhnovich N, Szukalska G, Banerjee B, Hilinski MK, Lannigan DA, Stukenberg PT, Derewenda ZS Biochemistry. 2012 Aug 21;51(33):6499-510. Epub 2012 Aug 6. PMID:22846040<ref>PMID:22846040</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3ubd" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
-	*[[Ribosomal protein S6 kinase\|Ribosomal protein S6 kinase]]	+	*[[Ribosomal protein S6 kinase 3D structures\|Ribosomal protein S6 kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 18:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice]]~~	+	[[Category: Mus musculus]]
-	~~[[Category: Non-specific serine/threonine protein kinase~~]]	+	[[Category: Derewenda U]]
-	[[Category: Derewenda, U]]	+	[[Category: Derewenda ZS]]
-	[[Category: Derewenda~~, Z S~~]]	+	[[Category: Utepbergenov D]]
-	[[Category: Utepbergenov, D]]	+
-	~~[[Category: Induced fit]]~~	+
-	~~[[Category: Kinase-inhibitor complex]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 06:06, 13 July 2022

2022-07-13T06:06:13Z

←Older revision		Revision as of 06:06, 13 July 2022
Line 1:		Line 1:

	==Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101==		==Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101==
-	<StructureSection load='3ubd' size='340' side='right' caption='[[3ubd]], [[Resolution\|resolution]] 1.53Å' scene=''>	+	<StructureSection load='3ubd' size='340' side='right'caption='[[3ubd]], [[Resolution\|resolution]] 1.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ubd]] 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=3UBD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3UBD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ubd]] is a 1 chain structure with sequence from [https://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=3UBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UBD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SL0:5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3,4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SL0:5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3,4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mapkapk1b, Rps6ka-rs1, Rps6ka3, Rsk2 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mapkapk1b, Rps6ka-rs1, Rps6ka3, Rsk2 ([https://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'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [~~http~~://pdbe.org/3ubd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3ubd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubd 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=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [https://pdbe.org/3ubd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [https://www.ebi.ac.uk/pdbsum/3ubd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubd 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 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3ubd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ubd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ribosomal protein S6 kinase\|Ribosomal protein S6 kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 10:02, 8 November 2017

2017-11-08T10:02:00Z

←Older revision		Revision as of 10:02, 8 November 2017
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3ubd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ubd" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Ribosomal protein S6 kinase\|Ribosomal protein S6 kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:08, 4 August 2016

2016-08-04T10:08:55Z

←Older revision		Revision as of 10:08, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101==		==Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101==
	<StructureSection load='3ubd' size='340' side='right' caption='[[3ubd]], [[Resolution\|resolution]] 1.53Å' scene=''>		<StructureSection load='3ubd' size='340' side='right' caption='[[3ubd]], [[Resolution\|resolution]] 1.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ubd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Mus_musculus Mus musculus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UBD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ubd]] 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=3UBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UBD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SL0:5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3,4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SL0:5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3,4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mapkapk1b, Rps6ka-rs1, Rps6ka3, Rsk2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 ~~Mus musculus~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mapkapk1b, Rps6ka-rs1, Rps6ka3, 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=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [http://www.ebi.ac.uk/pdbsum/3ubd 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=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [http://pdbe.org/3ubd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [http://www.ebi.ac.uk/pdbsum/3ubd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubd 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 3ubd" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Mus musculus~~]]	+	[[Category: Lk3 transgenic mice]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Derewenda, U]]		[[Category: Derewenda, U]]

OCA at 08:43, 24 December 2014

2014-12-24T08:43:36Z

←Older revision		Revision as of 08:43, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3ubd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UBD FirstGlance]. <br>		<table><tr><td colspan='2'>[[3ubd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UBD FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SL0:5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3,4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SL0:5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3,4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mapkapk1b, Rps6ka-rs1, Rps6ka3, Rsk2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mapkapk1b, Rps6ka-rs1, Rps6ka3, Rsk2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [http://www.ebi.ac.uk/pdbsum/3ubd 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=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [http://www.ebi.ac.uk/pdbsum/3ubd 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 25:		Line 27:
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Derewenda, U.]]	+	[[Category: Derewenda, U]]
-	[[Category: Derewenda, Z S.]]	+	[[Category: Derewenda, Z S]]
-	[[Category: Utepbergenov, D.]]	+	[[Category: Utepbergenov, D]]
	[[Category: Induced fit]]		[[Category: Induced fit]]
	[[Category: Kinase-inhibitor complex]]		[[Category: Kinase-inhibitor complex]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:23, 11 June 2014

2014-06-11T09:23:51Z

←Older revision		Revision as of 09:23, 11 June 2014
Line 1:		Line 1:
-	[[~~Image:~~3ubd.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101==
		+	<StructureSection load='3ubd' size='340' side='right' caption='[[3ubd]], [[Resolution\|resolution]] 1.53Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3ubd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UBD FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SL0:5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-4-OXO-4H-CHROMEN-3-YL+3,4-DI-O-ACETYL-6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>SL0</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mapkapk1b, Rps6ka-rs1, Rps6ka3, Rsk2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ubd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ubd RCSB], [http://www.ebi.ac.uk/pdbsum/3ubd PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The p90 ribosomal S6 family of kinases (RSK) are potential drug targets, due to their involvement in cancer and other pathologies. There are currently only two known selective inhibitors of RSK, but the basis for selectivity is not known. One of these inhibitors is a naturally occurring kaempferol-alpha-l-diacetylrhamnoside, SL0101. Here, we report the crystal structure of the complex of the N-terminal kinase domain of the RSK2 isoform with SL0101 at 1.5 A resolution. The refined atomic model reveals unprecedented structural reorganization of the protein moiety, as compared to the nucleotide-bound form. The entire N-lobe, the hinge region, and the alphaD-helix undergo dramatic conformational changes resulting in a rearrangement of the nucleotide binding site with concomitant formation of a highly hydrophobic pocket spatially suited to accommodate SL0101. These unexpected results will be invaluable in further optimization of the SL0101 scaffold as a promising lead for a novel class of kinase inhibitors.

-	~~{{STRUCTURE_3ubd\| PDB=3ubd \| SCENE= }}~~	+	Insights into the Inhibition of the p90 Ribosomal S6 Kinase (RSK) by the Flavonol Glycoside SL0101 from the 1.5 A Crystal Structure of the N-Terminal Domain of RSK2 with Bound Inhibitor.,Utepbergenov D, Derewenda U, Olekhnovich N, Szukalska G, Banerjee B, Hilinski MK, Lannigan DA, Stukenberg PT, Derewenda ZS Biochemistry. 2012 Aug 21;51(33):6499-510. Epub 2012 Aug 6. PMID:22846040<ref>PMID:22846040</ref>

-	~~===Structure~~ of ~~N-terminal domain~~ of ~~RSK2 kinase in complex with flavonoid glycoside SL0101===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22846040}}~~	+	==See Also==
-		+	*[[Ribosomal protein S6 kinase\|Ribosomal protein S6 kinase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~3ubd~~]] ~~is a 1 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBD OCA].~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 05:23, 5 September 2012

2012-09-05T05:23:29Z

←Older revision		Revision as of 05:23, 5 September 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3ubd.jpg\|left\|200px]]

-	~~The entry~~ 3ubd ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_3ubd\| PDB=3ubd \| SCENE= }}

-	~~Authors: Utepbergenov, D., Derewenda, U., Derewenda, Z.S.~~	+	===Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101===

-	~~Description:~~ Structure ~~of N~~-~~terminal domain of RSK2~~ kinase in complex ~~with flavonoid glycoside SL0101~~	+	{{ABSTRACT_PUBMED_22846040}}
		+
		+	==About this Structure==
		+	[[3ubd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBD OCA].
		+	[[Category: Mus musculus]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Derewenda, U.]]
		+	[[Category: Derewenda, Z S.]]
		+	[[Category: Utepbergenov, D.]]
		+	[[Category: Induced fit]]
		+	[[Category: Kinase-inhibitor complex]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:28, 11 April 2012

2012-04-11T06:28:25Z

←Older revision		Revision as of 06:28, 11 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3ubd is ON HOLD	+	The entry 3ubd is ON HOLD until Paper Publication

	Authors: Utepbergenov, D., Derewenda, U., Derewenda, Z.S.		Authors: Utepbergenov, D., Derewenda, U., Derewenda, Z.S.

	Description: Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101		Description: Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101

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

2011-11-02T08:00:23Z

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

←Older revision

Revision as of 08:00, 2 November 2011

OCA: New page: '''Unreleased structure''' The entry 3ubd is ON HOLD Authors: Utepbergenov, D., Derewenda, U., Derewenda, Z.S. Description: Structure of N-terminal domain of RSK2 kinase in complex wit...

2011-11-02T08:00:21Z

New page: '''Unreleased structure''' The entry 3ubd is ON HOLD Authors: Utepbergenov, D., Derewenda, U., Derewenda, Z.S. Description: Structure of N-terminal domain of RSK2 kinase in complex wit...

New page

'''Unreleased structure'''

The entry 3ubd is ON HOLD

Authors: Utepbergenov, D., Derewenda, U., Derewenda, Z.S.

Description: Structure of N-terminal domain of RSK2 kinase in complex with flavonoid glycoside SL0101