7oai - Revision history

OCA at 12:48, 1 February 2024

2024-02-01T12:48:16Z

←Older revision		Revision as of 12:48, 1 February 2024
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	<StructureSection load='7oai' size='340' side='right'caption='[[7oai]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='7oai' size='340' side='right'caption='[[7oai]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7oai]] is a 4 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=7OAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OAI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7oai]] is a 4 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=7OAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OAI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=V5W:4-(Cyclopentylamino)-2-[(2,5-dichlorophenyl)methylamino]-N-[3-(2-oxo-1,3-oxazolidin-3-yl)propyl]pyrimidine-5-carboxamide'>V5W</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]] 2.3Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASK, LIN2 ([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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=V5W:4-(Cyclopentylamino)-2-[(2,5-dichlorophenyl)methylamino]-N-[3-(2-oxo-1,3-oxazolidin-3-yl)propyl]pyrimidine-5-carboxamide'>V5W</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=7oai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oai OCA], [https://pdbe.org/7oai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oai RCSB], [https://www.ebi.ac.uk/pdbsum/7oai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oai 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=7oai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oai OCA], [https://pdbe.org/7oai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oai RCSB], [https://www.ebi.ac.uk/pdbsum/7oai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oai ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/CSKP_HUMAN CSKP_HUMAN]] Defects in CASK are the cause of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:[https://omim.org/entry/300749 300749]]. A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Patients with mental retardation X-linked CASK-related can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus.<ref>PMID:19165920</ref> Defects in CASK are the cause of FG syndrome type 4 (FGS4) [MIM:[https://omim.org/entry/300422 300422]]. FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.<ref>PMID:19200522</ref>	+	[https://www.uniprot.org/uniprot/CSKP_HUMAN CSKP_HUMAN] Defects in CASK are the cause of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:[https://omim.org/entry/300749 300749]. A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Patients with mental retardation X-linked CASK-related can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus.<ref>PMID:19165920</ref> Defects in CASK are the cause of FG syndrome type 4 (FGS4) [MIM:[https://omim.org/entry/300422 300422]. FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.<ref>PMID:19200522</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/CSKP_HUMAN CSKP_HUMAN]] Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TRB1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1.	+	[https://www.uniprot.org/uniprot/CSKP_HUMAN CSKP_HUMAN] Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TRB1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Chaikuad A]]
-	[[Category: Chaikuad, A]]	+	[[Category: Knapp S]]
-	[[Category: Knapp, S]]	+
-	~~[[Category: Structural genomic]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Pseudokinase]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 16:01, 3 November 2021

2021-11-03T16:01:44Z

←Older revision		Revision as of 16:01, 3 November 2021
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	==Crystal structure of pseudokinase CASK in complex with PFE-PKIS12==		==Crystal structure of pseudokinase CASK in complex with PFE-PKIS12==
-	<StructureSection load='7oai' size='340' side='right'caption='[[7oai]]' scene=''>	+	<StructureSection load='7oai' size='340' side='right'caption='[[7oai]], [[Resolution\|resolution]] 2.30Å' 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=7OAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OAI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7oai]] is a 4 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=7OAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OAI 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=7oai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oai OCA], [https://pdbe.org/7oai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oai RCSB], [https://www.ebi.ac.uk/pdbsum/7oai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oai 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=V5W:4-(Cyclopentylamino)-2-[(2,5-dichlorophenyl)methylamino]-N-[3-(2-oxo-1,3-oxazolidin-3-yl)propyl]pyrimidine-5-carboxamide'>V5W</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASK, LIN2 ([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=7oai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oai OCA], [https://pdbe.org/7oai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oai RCSB], [https://www.ebi.ac.uk/pdbsum/7oai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oai ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/CSKP_HUMAN CSKP_HUMAN]] Defects in CASK are the cause of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:[https://omim.org/entry/300749 300749]]. A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Patients with mental retardation X-linked CASK-related can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus.<ref>PMID:19165920</ref> Defects in CASK are the cause of FG syndrome type 4 (FGS4) [MIM:[https://omim.org/entry/300422 300422]]. FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.<ref>PMID:19200522</ref>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/CSKP_HUMAN CSKP_HUMAN]] Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TRB1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	CASK (Ca(2+)/calmodulin-dependent Ser/Thr kinase) is a member of the MAGUK (membrane-associated guanylate kinase) family that functions as neurexin kinases with roles implicated in neuronal synapses and trafficking. The lack of a canonical DFG motif, which is altered to GFG in CASK, led to the classification as a pseudokinase. However, functional studies revealed that CASK can still phosphorylate substrates in the absence of divalent metals. CASK dysfunction has been linked to many diseases, including colorectal cancer, Parkinson's disease, and X-linked mental retardation, suggesting CASK as a potential drug target. Here, we exploited structure-based design for the development of highly potent and selective CASK inhibitors based on 2,4-diaminopyrimidine-5-carboxamides targeting an unusual pocket created by the GFG motif. The presented inhibitor design offers a more general strategy for the development of pseudokinase ligands that harbor unusual sequence motifs. It also provides a first chemical probe for studying the biological roles of CASK.
		+
		+	Design and Development of a Chemical Probe for Pseudokinase Ca(2+)/calmodulin-Dependent Ser/Thr Kinase.,Russ N, Schroder M, Berger BT, Mandel S, Aydogan Y, Mauer S, Pohl C, Drewry DH, Chaikuad A, Muller S, Knapp S J Med Chem. 2021 Oct 14;64(19):14358-14376. doi: 10.1021/acs.jmedchem.1c00845., Epub 2021 Sep 20. PMID:34543009<ref>PMID:34543009</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7oai" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chaikuad A]]	+	[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Knapp S]]	+	[[Category: Chaikuad, A]]
		+	[[Category: Knapp, S]]
		+	[[Category: Structural genomic]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Pseudokinase]]
		+	[[Category: Sgc]]
		+	[[Category: Transferase]]

OCA at 10:11, 19 May 2021

2021-05-19T10:11:38Z

←Older revision		Revision as of 10:11, 19 May 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7oai is ON HOLD~~	+	==Crystal structure of pseudokinase CASK in complex with PFE-PKIS12==
-		+	<StructureSection load='7oai' size='340' side='right'caption='[[7oai]]' scene=''>
-	~~Authors: Chaikuad, A., 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=7OAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OAI FirstGlance]. <br>
-	~~Description:~~ Crystal structure of pseudokinase CASK in complex with PFE-PKIS12	+	</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=7oai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oai OCA], [https://pdbe.org/7oai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oai RCSB], [https://www.ebi.ac.uk/pdbsum/7oai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oai ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Chaikuad~~, A]]	+	__TOC__
-	[[Category: ~~Knapp, S~~]]	+	</StructureSection>
-	[[Category: ~~Structural Genomics Consortium (Sgc)~~]]	+	[[Category: Large Structures]]
		+	[[Category: Chaikuad A]]
		+	[[Category: Knapp S]]

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

2021-04-28T04:27:07Z

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

←Older revision

Revision as of 04:27, 28 April 2021

OCA: New page: '''Unreleased structure''' The entry 7oai is ON HOLD Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of pseudokinase CASK in compl...

2021-04-28T04:27:06Z

New page: '''Unreleased structure''' The entry 7oai is ON HOLD Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of pseudokinase CASK in compl...

New page

'''Unreleased structure'''

The entry 7oai is ON HOLD

Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC)

Description: Crystal structure of pseudokinase CASK in complex with PFE-PKIS12
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Knapp, S]]
[[Category: Structural Genomics Consortium (Sgc)]]