OCA at 23:13, 27 December 2023

OCA — Wed, 27 Dec 2023 23:13:45 GMT

←Older revision		Revision as of 23:13, 27 December 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8pqc ~~is ON HOLD until Paper Publication~~	+	==c-KIT kinase domain in complex with avapritinib derivative 9==
-		+	<StructureSection load='8pqc' size='340' side='right'caption='[[8pqc]], [[Resolution\|resolution]] 1.77Å' scene=''>
-	~~Authors~~: ~~Teuber~~, A., ~~Kleinboelting~~, S.B., ~~Mueller~~, M.P., ~~Rauh~~, D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[8pqc]] 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=8PQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PQC FirstGlance]. <br>
-	~~Description~~: c-KIT kinase domain in ~~complex with avapritinib derivative 9~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.77Å</td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9OO:(1~{S})-~{N}-ethyl-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine'>9OO</scene></td></tr>
-	[[Category: ~~Kleinboelting, S.B~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8pqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pqc OCA], [https://pdbe.org/8pqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pqc RCSB], [https://www.ebi.ac.uk/pdbsum/8pqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pqc ProSAT]</span></td></tr>
-	[[Category: ~~Teuber, A~~]]	+	</table>
-	[[Category: Mueller~~, M.P~~]]	+	== Disease ==
-	[[Category: Rauh, D]]	+	[https://www.uniprot.org/uniprot/KIT_HUMAN KIT_HUMAN] Defects in KIT are a cause of piebald trait (PBT) [MIM:[https://omim.org/entry/172800 172800]; also known as piebaldism. PBT is an autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.<ref>PMID:1376329</ref> <ref>PMID:1370874</ref> <ref>PMID:1717985</ref> <ref>PMID:7687267</ref> <ref>PMID:8680409</ref> <ref>PMID:9029028</ref> <ref>PMID:9450866</ref> <ref>PMID:9699740</ref> <ref>PMID:11074500</ref> Defects in KIT are a cause of gastrointestinal stromal tumor (GIST) [MIM:[https://omim.org/entry/606764 606764].<ref>PMID:9029028</ref> <ref>PMID:9697690</ref> <ref>PMID:9438854</ref> <ref>PMID:11505412</ref> <ref>PMID:15824741</ref> Defects in KIT have been associated with testicular germ cell tumor (TGCT) [MIM:[https://omim.org/entry/273300 273300]. A common solid malignancy in males. Germ cell tumors of the testis constitute 95% of all testicular neoplasms.<ref>PMID:9029028</ref> Defects in KIT are a cause of acute myelogenous leukemia (AML) [MIM:[https://omim.org/entry/601626 601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Note=Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase.<ref>PMID:9029028</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/KIT_HUMAN KIT_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.<ref>PMID:7520444</ref> <ref>PMID:9528781</ref> <ref>PMID:10397721</ref> <ref>PMID:12444928</ref> <ref>PMID:12878163</ref> <ref>PMID:12511554</ref> <ref>PMID:17904548</ref> <ref>PMID:19265199</ref> <ref>PMID:21640708</ref> <ref>PMID:21135090</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Kleinboelting SB]]
		+	[[Category: Mueller MP]]
		+	[[Category: Rauh D]]
		+	[[Category: Teuber A]]

OCA at 09:06, 2 August 2023

OCA — Wed, 02 Aug 2023 09:06:59 GMT

←Older revision		Revision as of 09:06, 2 August 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8pqc is ON HOLD	+	The entry 8pqc is ON HOLD until Paper Publication

	Authors: Teuber, A., Kleinboelting, S.B., Mueller, M.P., Rauh, D.		Authors: Teuber, A., Kleinboelting, S.B., Mueller, M.P., Rauh, D.

OCA: Protected "8pqc" [edit=sysop:move=sysop]

OCA — Wed, 19 Jul 2023 04:54:02 GMT

Protected "8pqc" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:54, 19 July 2023

OCA: New page: '''Unreleased structure''' The entry 8pqc is ON HOLD Authors: Teuber, A., Kleinboelting, S.B., Mueller, M.P., Rauh, D. Description: c-KIT kinase domain in complex with avapritinib deri...

OCA — Wed, 19 Jul 2023 04:54:00 GMT

New page: '''Unreleased structure''' The entry 8pqc is ON HOLD Authors: Teuber, A., Kleinboelting, S.B., Mueller, M.P., Rauh, D. Description: c-KIT kinase domain in complex with avapritinib deri...

New page

'''Unreleased structure'''

The entry 8pqc is ON HOLD

Authors: Teuber, A., Kleinboelting, S.B., Mueller, M.P., Rauh, D.

Description: c-KIT kinase domain in complex with avapritinib derivative 9
[[Category: Unreleased Structures]]
[[Category: Kleinboelting, S.B]]
[[Category: Teuber, A]]
[[Category: Mueller, M.P]]
[[Category: Rauh, D]]

8pqc - Revision history

OCA at 23:13, 27 December 2023

OCA at 09:06, 2 August 2023

OCA: Protected "8pqc" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8pqc is ON HOLD Authors: Teuber, A., Kleinboelting, S.B., Mueller, M.P., Rauh, D. Description: c-KIT kinase domain in complex with avapritinib deri...