7up5 - Revision history

OCA at 07:22, 3 April 2024

OCA — Wed, 03 Apr 2024 07:22:41 GMT

←Older revision		Revision as of 07:22, 3 April 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7up5]] is a 2 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=7UP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UP5 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7up5]] is a 2 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=7UP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UP5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=O1R:(2M)-6-chloro-2-(5H-pyrrolo[3,2-d]pyrimidin-5-yl)pyridine-3-carbonitrile'>O1R</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=O1R:(2M)-6-chloro-2-(5H-pyrrolo[3,2-d]pyrimidin-5-yl)pyridine-3-carbonitrile'>O1R</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=7up5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7up5 OCA], [https://pdbe.org/7up5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7up5 RCSB], [https://www.ebi.ac.uk/pdbsum/7up5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7up5 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=7up5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7up5 OCA], [https://pdbe.org/7up5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7up5 RCSB], [https://www.ebi.ac.uk/pdbsum/7up5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7up5 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/KS6A5_HUMAN KS6A5_HUMAN]] Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.<ref>PMID:11909979</ref> <ref>PMID:12569367</ref> <ref>PMID:12628924</ref> <ref>PMID:12763138</ref> <ref>PMID:12773393</ref> <ref>PMID:15010469</ref> <ref>PMID:18511904</ref> <ref>PMID:9687510</ref> <ref>PMID:9873047</ref>	+	[https://www.uniprot.org/uniprot/KS6A5_HUMAN KS6A5_HUMAN] Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.<ref>PMID:11909979</ref> <ref>PMID:12569367</ref> <ref>PMID:12628924</ref> <ref>PMID:12763138</ref> <ref>PMID:12773393</ref> <ref>PMID:15010469</ref> <ref>PMID:18511904</ref> <ref>PMID:9687510</ref> <ref>PMID:9873047</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	We describe the identification and characterization of a series of covalent inhibitors of the C-terminal kinase domain (CTKD) of MSK1. The initial hit was identified via a high-throughput screening and represents a rare example of a covalent inhibitor which acts via an SNAr reaction of a 2,5-dichloropyrimidine with a cysteine residue (Cys440). The covalent mechanism of action was supported by in vitro biochemical experiments and was confirmed by mass spectrometry. Ultimately, the displacement of the 2-chloro moiety was confirmed by crystallization of an inhibitor with the CTKD. We also disclose the crystal structures of three compounds from this series bound to the CTKD of MSK1, in addition to the crystal structures of two unrelated RSK2 covalent inhibitors bound to the CTKD of MSK1.	+

-	Discovery and Characterization of a Novel Series of Chloropyrimidines as Covalent Inhibitors of the Kinase MSK1.,Hall A, Abendroth J, Bolejack MJ, Ceska T, Dell'Aiera S, Ellis V, Fox D 3rd, Francois C, Muruthi MM, Prevel C, Poullennec K, Romanov S, Valade A, Vanbellinghen A, Yano J, Geraerts M ACS Med Chem Lett. 2022 Jun 25;13(7):1099-1108. doi:, 10.1021/acsmedchemlett.2c00134. eCollection 2022 Jul 14. PMID:35859861<ref>PMID:35859861</ref>	+	==See Also==
-		+	*[[Ribosomal protein S6 kinase 3D structures\|Ribosomal protein S6 kinase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 7up5" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>

OCA at 03:56, 8 September 2022

OCA — Thu, 08 Sep 2022 03:56:56 GMT

←Older revision		Revision as of 03:56, 8 September 2022
Line 3:		Line 3:
	<StructureSection load='7up5' size='340' side='right'caption='[[7up5]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='7up5' size='340' side='right'caption='[[7up5]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7up5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UP5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7up5]] is a 2 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=7UP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UP5 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=O1R:(2M)-6-chloro-2-(5H-pyrrolo[3,2-d]pyrimidin-5-yl)pyridine-3-carbonitrile'>O1R</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=O1R:(2M)-6-chloro-2-(5H-pyrrolo[3,2-d]pyrimidin-5-yl)pyridine-3-carbonitrile'>O1R</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=7up5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7up5 OCA], [https://pdbe.org/7up5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7up5 RCSB], [https://www.ebi.ac.uk/pdbsum/7up5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7up5 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=7up5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7up5 OCA], [https://pdbe.org/7up5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7up5 RCSB], [https://www.ebi.ac.uk/pdbsum/7up5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7up5 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/KS6A5_HUMAN KS6A5_HUMAN]] Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.<ref>PMID:11909979</ref> <ref>PMID:12569367</ref> <ref>PMID:12628924</ref> <ref>PMID:12763138</ref> <ref>PMID:12773393</ref> <ref>PMID:15010469</ref> <ref>PMID:18511904</ref> <ref>PMID:9687510</ref> <ref>PMID:9873047</ref>	+	[[https://www.uniprot.org/uniprot/KS6A5_HUMAN KS6A5_HUMAN]] Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.<ref>PMID:11909979</ref> <ref>PMID:12569367</ref> <ref>PMID:12628924</ref> <ref>PMID:12763138</ref> <ref>PMID:12773393</ref> <ref>PMID:15010469</ref> <ref>PMID:18511904</ref> <ref>PMID:9687510</ref> <ref>PMID:9873047</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Edwards TE]]
-	[[Category: Edwards~~, T E~~]]	+	[[Category: Hall A]]
-	[[Category: Hall, A]]	+	[[Category: Yano JK]]
-	[[Category: Yano~~, J K]]~~	+
-	~~[[Category: C-terminal domain]]~~	+
-	~~[[Category: Msk1]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 05:03, 3 August 2022

OCA — Wed, 03 Aug 2022 05:03:58 GMT

←Older revision		Revision as of 05:03, 3 August 2022
Line 1:		Line 1:

	==Crystal structure of C-terminal Domain of MSK1 in complex with covalently bound pyrrolopyrimidine compound 23 (co-crystal)==		==Crystal structure of C-terminal Domain of MSK1 in complex with covalently bound pyrrolopyrimidine compound 23 (co-crystal)==
-	<StructureSection load='7up5' size='340' side='right'caption='[[7up5]]' scene=''>	+	<StructureSection load='7up5' size='340' side='right'caption='[[7up5]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UP5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7up5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UP5 FirstGlance]. <br>
-	</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=7up5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7up5 OCA], [https://pdbe.org/7up5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7up5 RCSB], [https://www.ebi.ac.uk/pdbsum/7up5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7up5 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=O1R:(2M)-6-chloro-2-(5H-pyrrolo[3,2-d]pyrimidin-5-yl)pyridine-3-carbonitrile'>O1R</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=7up5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7up5 OCA], [https://pdbe.org/7up5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7up5 RCSB], [https://www.ebi.ac.uk/pdbsum/7up5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7up5 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/KS6A5_HUMAN KS6A5_HUMAN]] Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.<ref>PMID:11909979</ref> <ref>PMID:12569367</ref> <ref>PMID:12628924</ref> <ref>PMID:12763138</ref> <ref>PMID:12773393</ref> <ref>PMID:15010469</ref> <ref>PMID:18511904</ref> <ref>PMID:9687510</ref> <ref>PMID:9873047</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We describe the identification and characterization of a series of covalent inhibitors of the C-terminal kinase domain (CTKD) of MSK1. The initial hit was identified via a high-throughput screening and represents a rare example of a covalent inhibitor which acts via an SNAr reaction of a 2,5-dichloropyrimidine with a cysteine residue (Cys440). The covalent mechanism of action was supported by in vitro biochemical experiments and was confirmed by mass spectrometry. Ultimately, the displacement of the 2-chloro moiety was confirmed by crystallization of an inhibitor with the CTKD. We also disclose the crystal structures of three compounds from this series bound to the CTKD of MSK1, in addition to the crystal structures of two unrelated RSK2 covalent inhibitors bound to the CTKD of MSK1.
		+
		+	Discovery and Characterization of a Novel Series of Chloropyrimidines as Covalent Inhibitors of the Kinase MSK1.,Hall A, Abendroth J, Bolejack MJ, Ceska T, Dell'Aiera S, Ellis V, Fox D 3rd, Francois C, Muruthi MM, Prevel C, Poullennec K, Romanov S, Valade A, Vanbellinghen A, Yano J, Geraerts M ACS Med Chem Lett. 2022 Jun 25;13(7):1099-1108. doi:, 10.1021/acsmedchemlett.2c00134. eCollection 2022 Jul 14. PMID:35859861<ref>PMID:35859861</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7up5" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Edwards TE]]	+	[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Hall A]]	+	[[Category: Edwards, T E]]
-	[[Category: Yano JK]]	+	[[Category: Hall, A]]
		+	[[Category: Yano, J K]]
		+	[[Category: C-terminal domain]]
		+	[[Category: Msk1]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase]]

OCA at 16:14, 6 July 2022

OCA — Wed, 06 Jul 2022 16:14:46 GMT

←Older revision		Revision as of 16:14, 6 July 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7up5 is ON HOLD until Paper Publication~~	+	==Crystal structure of C-terminal Domain of MSK1 in complex with covalently bound pyrrolopyrimidine compound 23 (co-crystal)==
-		+	<StructureSection load='7up5' size='340' side='right'caption='[[7up5]]' scene=''>
-	~~Authors: Yano, J.K., Edwards, T.E., Hall, A.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UP5 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of C-terminal Domain of MSK1 in complex with covalently bound pyrrolopyrimidine compound 23 (co-crystal)	+	</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=7up5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7up5 OCA], [https://pdbe.org/7up5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7up5 RCSB], [https://www.ebi.ac.uk/pdbsum/7up5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7up5 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Hall, A~~]]	+	__TOC__
-	[[Category: ~~Edwards, T.E~~]]	+	</StructureSection>
-	[[Category: Yano~~, J.K~~]]	+	[[Category: Large Structures]]
		+	[[Category: Edwards TE]]
		+	[[Category: Hall A]]
		+	[[Category: Yano JK]]

OCA at 09:01, 18 May 2022

OCA — Wed, 18 May 2022 09:01:20 GMT

←Older revision		Revision as of 09:01, 18 May 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7up5 is ON HOLD	+	The entry 7up5 is ON HOLD until Paper Publication

	Authors: Yano, J.K., Edwards, T.E., Hall, A.		Authors: Yano, J.K., Edwards, T.E., Hall, A.

OCA: Protected "7up5" [edit=sysop:move=sysop]

OCA — Thu, 21 Apr 2022 01:38:22 GMT

Protected "7up5" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:38, 21 April 2022

OCA: New page: '''Unreleased structure''' The entry 7up5 is ON HOLD Authors: Yano, J.K., Edwards, T.E., Hall, A. Description: Crystal structure of C-terminal Domain of MSK1 in complex with covalently...

OCA — Thu, 21 Apr 2022 01:38:21 GMT

New page: '''Unreleased structure''' The entry 7up5 is ON HOLD Authors: Yano, J.K., Edwards, T.E., Hall, A. Description: Crystal structure of C-terminal Domain of MSK1 in complex with covalently...

New page

'''Unreleased structure'''

The entry 7up5 is ON HOLD

Authors: Yano, J.K., Edwards, T.E., Hall, A.

Description: Crystal structure of C-terminal Domain of MSK1 in complex with covalently bound pyrrolopyrimidine compound 23 (co-crystal)
[[Category: Unreleased Structures]]
[[Category: Hall, A]]
[[Category: Edwards, T.E]]
[[Category: Yano, J.K]]