7b30 - Revision history

OCA at 12:21, 1 February 2024

2024-02-01T12:21:13Z

←Older revision		Revision as of 12:21, 1 February 2024
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	<StructureSection load='7b30' size='340' side='right'caption='[[7b30]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='7b30' size='340' side='right'caption='[[7b30]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7b30]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B30 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7b30]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B30 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=59T:8-[(TRANS-5-AMINO-1,3-DIOXAN-2-YL)METHYL]-6-[2-CHLORO-4-(6-METHYLPYRIDIN-2-YL)PHENYL]-2-(METHYLAMINO)PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE'>59T</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]] 2.1Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">STK24, MST3, STK3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=59T:8-[(TRANS-5-AMINO-1,3-DIOXAN-2-YL)METHYL]-6-[2-CHLORO-4-(6-METHYLPYRIDIN-2-YL)PHENYL]-2-(METHYLAMINO)PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE'>59T</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=7b30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b30 OCA], [https://pdbe.org/7b30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b30 RCSB], [https://www.ebi.ac.uk/pdbsum/7b30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b30 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=7b30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b30 OCA], [https://pdbe.org/7b30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b30 RCSB], [https://www.ebi.ac.uk/pdbsum/7b30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b30 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/STK24_HUMAN STK24_HUMAN]] Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. Regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.<ref>PMID:16314523</ref> <ref>PMID:17046825</ref> <ref>PMID:19604147</ref> <ref>PMID:19855390</ref> <ref>PMID:19782762</ref>	+	[https://www.uniprot.org/uniprot/STK24_HUMAN STK24_HUMAN] Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. Regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.<ref>PMID:16314523</ref> <ref>PMID:17046825</ref> <ref>PMID:19604147</ref> <ref>PMID:19855390</ref> <ref>PMID:19782762</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7b30" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7b30" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Joerger AC]]
-	[[Category: Joerger~~, A C~~]]	+	[[Category: Knapp S]]
-	[[Category: Knapp, S]]	+	[[Category: Rak M]]
-	[[Category: Rak, M]]	+	[[Category: Tesch R]]
-	~~[[Category: Structural genomic~~]]	+
-	[[Category: Tesch, R]]	+
-	~~[[Category: Kinase inhibitor]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Sik2 inhibitor]]~~	+
-	~~[[Category: Structure-based drug design]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:46, 25 June 2021

2021-06-25T07:46:09Z

←Older revision		Revision as of 07:46, 25 June 2021
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	==MST3 in complex with compound G-5555==		==MST3 in complex with compound G-5555==
-	<StructureSection load='7b30' size='340' side='right'caption='[[7b30]]' scene=''>	+	<StructureSection load='7b30' size='340' side='right'caption='[[7b30]], [[Resolution\|resolution]] 2.10Å' 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=7B30 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7B30 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7b30]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B30 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7b30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b30 OCA], [~~http~~://pdbe.org/7b30 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7b30 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7b30 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7b30 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=59T:8-[(TRANS-5-AMINO-1,3-DIOXAN-2-YL)METHYL]-6-[2-CHLORO-4-(6-METHYLPYRIDIN-2-YL)PHENYL]-2-(METHYLAMINO)PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE'>59T</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">STK24, MST3, STK3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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=7b30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b30 OCA], [https://pdbe.org/7b30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b30 RCSB], [https://www.ebi.ac.uk/pdbsum/7b30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b30 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/STK24_HUMAN STK24_HUMAN]] Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. Regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.<ref>PMID:16314523</ref> <ref>PMID:17046825</ref> <ref>PMID:19604147</ref> <ref>PMID:19855390</ref> <ref>PMID:19782762</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Salt-inducible kinases (SIKs) are key metabolic regulators. The imbalance in SIK function is associated with the development of diverse cancers, including breast, gastric, and ovarian cancers. Chemical tools to clarify the roles of SIK in different diseases are, however, sparse and are generally characterized by poor kinome-wide selectivity. Here, we have adapted the pyrido[2,3-d]pyrimidin-7-one-based p21-activated kinase (PAK) inhibitor G-5555 for the targeting of SIK, by exploiting differences in the back-pocket region of these kinases. Optimization was supported by high-resolution crystal structures of G-5555 bound to the known off-targets, MST3 and MST4, leading to a chemical probe, MRIA9, with dual SIK/PAK activity and excellent selectivity over other kinases. Furthermore, we show that MRIA9 sensitizes ovarian cancer cells to treatment with the mitotic agent paclitaxel, confirming earlier data from genetic knockdown studies and suggesting a combination therapy with SIK inhibitors and paclitaxel for the treatment of paclitaxel-resistant ovarian cancer.
		+
		+	Structure-Based Design of Selective Salt-Inducible Kinase Inhibitors.,Tesch R, Rak M, Raab M, Berger LM, Kronenberger T, Joerger AC, Berger BT, Abdi I, Hanke T, Poso A, Strebhardt K, Sanhaji M, Knapp S J Med Chem. 2021 Jun 24;64(12):8142-8160. doi: 10.1021/acs.jmedchem.0c02144. Epub, 2021 Jun 4. PMID:34086472<ref>PMID:34086472</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7b30" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Joerger AC]]	+	[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Knapp S]]	+	[[Category: Joerger, A C]]
-	[[Category: Rak M]]	+	[[Category: Knapp, S]]
-	[[Category: Tesch R]]	+	[[Category: Rak, M]]
		+	[[Category: Structural genomic]]
		+	[[Category: Tesch, R]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Sgc]]
		+	[[Category: Sik2 inhibitor]]
		+	[[Category: Structure-based drug design]]
		+	[[Category: Transferase]]

OCA at 12:34, 16 December 2020

2020-12-16T12:34:12Z

←Older revision		Revision as of 12:34, 16 December 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7b30 ~~is ON HOLD~~	+	==MST3 in complex with compound G-5555==
-		+	<StructureSection load='7b30' size='340' side='right'caption='[[7b30]]' scene=''>
-	~~Authors~~: ~~Tesch, R~~., ~~Rak~~, M., ~~Joerger, A~~.C., ~~Knapp, S~~., ~~Structural Genomics Consortium (SGC)~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B30 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7B30 FirstGlance]. <br>
-	~~Description~~: ~~MST3 in complex with compound G~~-~~5555~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7b30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b30 OCA], [http://pdbe.org/7b30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7b30 RCSB], [http://www.ebi.ac.uk/pdbsum/7b30 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7b30 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Rak, M]]~~	+	__TOC__
-	~~[[Category: Tesch, R~~]]	+	</StructureSection>
-	[[Category: Knapp, S]]	+	[[Category: Large Structures]]
-	[[Category: ~~Joerger, A.C~~]]	+	[[Category: Joerger AC]]
-	[[Category: ~~Structural Genomics Consortium (Sgc)~~]]	+	[[Category: Knapp S]]
		+	[[Category: Rak M]]
		+	[[Category: Tesch R]]

OCA: Protected "7b30" [edit=sysop:move=sysop]

2020-12-09T05:00:31Z

Protected "7b30" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:00, 9 December 2020

OCA: New page: '''Unreleased structure''' The entry 7b30 is ON HOLD Authors: Tesch, R., Rak, M., Joerger, A.C., Knapp, S., Structural Genomics Consortium (SGC) Description: MST3 in complex with compo...

2020-12-09T05:00:30Z

New page: '''Unreleased structure''' The entry 7b30 is ON HOLD Authors: Tesch, R., Rak, M., Joerger, A.C., Knapp, S., Structural Genomics Consortium (SGC) Description: MST3 in complex with compo...

New page

'''Unreleased structure'''

The entry 7b30 is ON HOLD

Authors: Tesch, R., Rak, M., Joerger, A.C., Knapp, S., Structural Genomics Consortium (SGC)

Description: MST3 in complex with compound G-5555
[[Category: Unreleased Structures]]
[[Category: Rak, M]]
[[Category: Tesch, R]]
[[Category: Knapp, S]]
[[Category: Joerger, A.C]]
[[Category: Structural Genomics Consortium (Sgc)]]