7que - Revision history

OCA at 13:23, 1 February 2024

2024-02-01T13:23:04Z

← Older revision		Revision as of 13:23, 1 February 2024
Line 1:		Line 1:

	==The STK17A (DRAK1) Kinase Domain Bound to CKJB68==		==The STK17A (DRAK1) Kinase Domain Bound to CKJB68==
	<StructureSection load='7que' size='340' side='right'caption='[[7que]]' scene=''>		<StructureSection load='7que' size='340' side='right'caption='[[7que]], [[Resolution\|resolution]] 2.40Å' 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=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE FirstGlance]. <br>		<table><tr><td colspan='2'>[[7que]] 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=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE 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=7que FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7que OCA], [https://pdbe.org/7que PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7que RCSB], [https://www.ebi.ac.uk/pdbsum/7que PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7que ProSAT]</span></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]] 2.4Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F7I:~{N}-(phenylmethyl)-7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.1^{2,6}.0^{17,20}]docosa-1(20),2(22),3,5,14(21),15,18-heptaene-5-carboxamide'>F7I</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=7que FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7que OCA], [https://pdbe.org/7que PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7que RCSB], [https://www.ebi.ac.uk/pdbsum/7que PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7que ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/ST17A_HUMAN ST17A_HUMAN] Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.<ref>PMID:21489989</ref> <ref>PMID:9786912</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Serine/threonine kinase 17A (death-associated protein kinase-related apoptosis-inducing protein kinase 1 horizontal line DRAK1) is a part of the death-associated protein kinase (DAPK) family and belongs to the so-called dark kinome. Thus, the current state of knowledge of the cellular function of DRAK1 and its involvement in pathophysiological processes is very limited. Recently, DRAK1 has been implicated in tumorigenesis of glioblastoma multiforme (GBM) and other cancers, but no selective inhibitors of DRAK1 are available yet. To this end, we optimized a pyrazolo[1,5-a]pyrimidine-based macrocyclic scaffold. Structure-guided optimization of this macrocyclic scaffold led to the development of CK156 (34), which displayed high in vitro potency (KD = 21 nM) and selectivity in kinomewide screens. Crystal structures demonstrated that CK156 (34) acts as a type I inhibitor. However, contrary to studies using genetic knockdown of DRAK1, we have seen the inhibition of cell growth of glioma cells in 2D and 3D culture only at low micromolar concentrations.

			Illuminating the Dark: Highly Selective Inhibition of Serine/Threonine Kinase 17A with Pyrazolo[1,5-a]pyrimidine-Based Macrocycles.,Kurz CG, Preuss F, Tjaden A, Cusack M, Amrhein JA, Chatterjee D, Mathea S, Berger LM, Berger BT, Kramer A, Weller M, Weiss T, Muller S, Knapp S, Hanke T J Med Chem. 2022 Jun 9;65(11):7799-7817. doi: 10.1021/acs.jmedchem.2c00173. Epub , 2022 May 24. PMID:35608370<ref>PMID:35608370</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7que" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Amrhein JA]]		[[Category: Amrhein JA]]

OCA at 11:05, 31 August 2022

2022-08-31T11:05:52Z

← Older revision		Revision as of 11:05, 31 August 2022
Line 1:		Line 1:

	==The STK17A (DRAK1) Kinase Domain Bound to CKJB68==		==The STK17A (DRAK1) Kinase Domain Bound to CKJB68==
	<StructureSection load='7que' size='340' side='right'caption='[[7que]]~~, [[Resolution\|resolution]] 2.40Å~~' scene=''>		<StructureSection load='7que' size='340' side='right'caption='[[7que]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[7que]] is a 2 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F7I:~{N}-(phenylmethyl)-7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.1^{2,6}.0^{17,20}]docosa-1(20),2(22),3,5,14(21),15,18-heptaene-5-carboxamide'>F7I</scene></td></tr>		</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=7que FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7que OCA], [https://pdbe.org/7que PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7que RCSB], [https://www.ebi.ac.uk/pdbsum/7que PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7que ProSAT]</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'>[https://proteopedia.org/fgij/fg.htm?mol=7que FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7que OCA], [https://pdbe.org/7que PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7que RCSB], [https://www.ebi.ac.uk/pdbsum/7que PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7que ProSAT]</span></td></tr>
	</table>		</table>
	~~== Function ==~~
	[[https://www.uniprot.org/uniprot/ST17A_HUMAN ST17A_HUMAN]] Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.<ref>PMID:21489989</ref> <ref>PMID:9786912</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Serine/threonine kinase 17A (death-associated protein kinase-related apoptosis-inducing protein kinase 1 horizontal line DRAK1) is a part of the death-associated protein kinase (DAPK) family and belongs to the so-called dark kinome. Thus, the current state of knowledge of the cellular function of DRAK1 and its involvement in pathophysiological processes is very limited. Recently, DRAK1 has been implicated in tumorigenesis of glioblastoma multiforme (GBM) and other cancers, but no selective inhibitors of DRAK1 are available yet. To this end, we optimized a pyrazolo[1,5-a]pyrimidine-based macrocyclic scaffold. Structure-guided optimization of this macrocyclic scaffold led to the development of CK156 (34), which displayed high in vitro potency (KD = 21 nM) and selectivity in kinomewide screens. Crystal structures demonstrated that CK156 (34) acts as a type I inhibitor. However, contrary to studies using genetic knockdown of DRAK1, we have seen the inhibition of cell growth of glioma cells in 2D and 3D culture only at low micromolar concentrations.

	Illuminating the Dark: Highly Selective Inhibition of Serine/Threonine Kinase 17A with Pyrazolo[1,5-a]pyrimidine-Based Macrocycles.,Kurz CG, Preuss F, Tjaden A, Cusack M, Amrhein JA, Chatterjee D, Mathea S, Berger LM, Berger BT, Kramer A, Weller M, Weiss T, Muller S, Knapp S, Hanke T J Med Chem. 2022 Jun 9;65(11):7799-7817. doi: 10.1021/acs.jmedchem.2c00173. Epub , 2022 May 24. PMID:35608370<ref>PMID:35608370</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 7que" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific serine/threonine protein kinase]]~~		[[Category: Amrhein JA]]
	[[Category: Amrhein~~, J A~~]]		[[Category: Chatterjee D]]
	[[Category: Chatterjee, D]]		[[Category: Dederer V]]
	[[Category: Dederer, V]]		[[Category: Hanke T]]
	[[Category: Hanke, T]]		[[Category: Knapp S]]
	[[Category: Knapp, S]]		[[Category: Kurz CG]]
	[[Category: Kurz~~, C G~~]]		[[Category: Mathea S]]
	[[Category: Mathea, S]]		[[Category: Preuss F]]
	[[Category: Preuss, F]]
	~~[[Category: Kinase small-molecule binder inhibitor macrocycle]]~~
	~~[[Category: Transferase~~]]

OCA at 05:12, 25 August 2022

2022-08-25T05:12:23Z

← Older revision		Revision as of 05:12, 25 August 2022
Line 1:		Line 1:

	==The STK17A (DRAK1) Kinase Domain Bound to CKJB68==		==The STK17A (DRAK1) Kinase Domain Bound to CKJB68==
	<StructureSection load='7que' size='340' side='right'caption='[[7que]]' scene=''>		<StructureSection load='7que' size='340' side='right'caption='[[7que]], [[Resolution\|resolution]] 2.40Å' 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=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE FirstGlance]. <br>		<table><tr><td colspan='2'>[[7que]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE 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=7que FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7que OCA], [https://pdbe.org/7que PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7que RCSB], [https://www.ebi.ac.uk/pdbsum/7que PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7que 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=F7I:~{N}-(phenylmethyl)-7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.1^{2,6}.0^{17,20}]docosa-1(20),2(22),3,5,14(21),15,18-heptaene-5-carboxamide'>F7I</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=7que FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7que OCA], [https://pdbe.org/7que PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7que RCSB], [https://www.ebi.ac.uk/pdbsum/7que PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7que ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[https://www.uniprot.org/uniprot/ST17A_HUMAN ST17A_HUMAN]] Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.<ref>PMID:21489989</ref> <ref>PMID:9786912</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Serine/threonine kinase 17A (death-associated protein kinase-related apoptosis-inducing protein kinase 1 horizontal line DRAK1) is a part of the death-associated protein kinase (DAPK) family and belongs to the so-called dark kinome. Thus, the current state of knowledge of the cellular function of DRAK1 and its involvement in pathophysiological processes is very limited. Recently, DRAK1 has been implicated in tumorigenesis of glioblastoma multiforme (GBM) and other cancers, but no selective inhibitors of DRAK1 are available yet. To this end, we optimized a pyrazolo[1,5-a]pyrimidine-based macrocyclic scaffold. Structure-guided optimization of this macrocyclic scaffold led to the development of CK156 (34), which displayed high in vitro potency (KD = 21 nM) and selectivity in kinomewide screens. Crystal structures demonstrated that CK156 (34) acts as a type I inhibitor. However, contrary to studies using genetic knockdown of DRAK1, we have seen the inhibition of cell growth of glioma cells in 2D and 3D culture only at low micromolar concentrations.

			Illuminating the Dark: Highly Selective Inhibition of Serine/Threonine Kinase 17A with Pyrazolo[1,5-a]pyrimidine-Based Macrocycles.,Kurz CG, Preuss F, Tjaden A, Cusack M, Amrhein JA, Chatterjee D, Mathea S, Berger LM, Berger BT, Kramer A, Weller M, Weiss T, Muller S, Knapp S, Hanke T J Med Chem. 2022 Jun 9;65(11):7799-7817. doi: 10.1021/acs.jmedchem.2c00173. Epub , 2022 May 24. PMID:35608370<ref>PMID:35608370</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7que" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Amrhein JA]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Chatterjee D]]		[[Category: Amrhein, J A]]
	[[Category: Dederer V]]		[[Category: Chatterjee, D]]
	[[Category: Hanke T]]		[[Category: Dederer, V]]
	[[Category: Knapp S]]		[[Category: Hanke, T]]
	[[Category: Kurz CG]]		[[Category: Knapp, S]]
	[[Category: Mathea S]]		[[Category: Kurz, C G]]
	[[Category: Preuss F]]		[[Category: Mathea, S]]
			[[Category: Preuss, F]]
			[[Category: Kinase small-molecule binder inhibitor macrocycle]]
			[[Category: Transferase]]

OCA at 07:03, 2 February 2022

2022-02-02T07:03:01Z

← Older revision		Revision as of 07:03, 2 February 2022
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	The ~~entry~~ 7que is ~~ON HOLD~~		==The STK17A (DRAK1) Kinase Domain Bound to CKJB68==
			<StructureSection load='7que' size='340' side='right'caption='[[7que]]' scene=''>
	~~Authors~~: ~~Mathea~~, S., ~~Preuss~~, F., ~~Chatterjee, D~~.~~, Dederer, V~~.~~, Kurz, C~~., ~~Hanke, T~~.~~, Knapp, S~~.		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUE FirstGlance]. <br>
	~~Description~~: ~~The STK17A (DRAK1) Kinase Domain Bound to CKjB68~~		</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=7que FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7que OCA], [https://pdbe.org/7que PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7que RCSB], [https://www.ebi.ac.uk/pdbsum/7que PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7que ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
	[[Category: ~~Knapp, S~~]]		__TOC__
	[[Category: ~~Mathea, S~~]]		</StructureSection>
	[[Category: Hanke, T]]		[[Category: Large Structures]]
	[[Category: ~~Kurz, C~~]]		[[Category: Amrhein JA]]
	[[Category: ~~Dederer, V~~]]		[[Category: Chatterjee D]]
	[[Category: ~~Chatterjee, D~~]]		[[Category: Dederer V]]
	[[Category: Preuss, F]]		[[Category: Hanke T]]
			[[Category: Knapp S]]
			[[Category: Kurz CG]]
			[[Category: Mathea S]]
			[[Category: Preuss F]]

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

2022-01-27T05:22:38Z

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

← Older revision	Revision as of 05:22, 27 January 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7que is ON HOLD Authors: Mathea, S., Preuss, F., Chatterjee, D., Dederer, V., Kurz, C., Hanke, T., Knapp, S. Description: The STK17A (DRAK1) Kinase...

2022-01-27T05:22:37Z

New page: '''Unreleased structure''' The entry 7que is ON HOLD Authors: Mathea, S., Preuss, F., Chatterjee, D., Dederer, V., Kurz, C., Hanke, T., Knapp, S. Description: The STK17A (DRAK1) Kinase...

New page

'''Unreleased structure'''

The entry 7que is ON HOLD

Authors: Mathea, S., Preuss, F., Chatterjee, D., Dederer, V., Kurz, C., Hanke, T., Knapp, S.

Description: The STK17A (DRAK1) Kinase Domain Bound to CKjB68
[[Category: Unreleased Structures]]
[[Category: Knapp, S]]
[[Category: Mathea, S]]
[[Category: Hanke, T]]
[[Category: Kurz, C]]
[[Category: Dederer, V]]
[[Category: Chatterjee, D]]
[[Category: Preuss, F]]