OCA at 13:38, 24 January 2024

2024-01-24T13:38:23Z

←Older revision		Revision as of 13:38, 24 January 2024
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	==Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently bound to the PH domain of Bruton's tyrosine kinase mutant R28C==		==Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently bound to the PH domain of Bruton's tyrosine kinase mutant R28C==
-	<StructureSection load='6yyg' size='340' side='right'caption='[[6yyg]]' scene=''>	+	<StructureSection load='6yyg' size='340' side='right'caption='[[6yyg]], [[Resolution\|resolution]] 1.95Å' 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=6YYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YYG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yyg]] 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=6YYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YYG 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=6yyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yyg OCA], [https://pdbe.org/6yyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yyg RCSB], [https://www.ebi.ac.uk/pdbsum/6yyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yyg 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]] 1.95Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=Q1B:5-(trifluoromethyloxy)-1,3-dihydroindol-2-one'>Q1B</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6yyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yyg OCA], [https://pdbe.org/6yyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yyg RCSB], [https://www.ebi.ac.uk/pdbsum/6yyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yyg ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/BTK_HUMAN BTK_HUMAN] Defects in BTK are the cause of X-linked agammaglobulinemia (XLA) [MIM:[https://omim.org/entry/300755 300755]; also known as X-linked agammaglobulinemia type 1 (AGMX1) or immunodeficiency type 1 (IMD1). XLA is a humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin.<ref>PMID:7880320</ref> <ref>PMID:8013627</ref> <ref>PMID:8162056</ref> <ref>PMID:8162018</ref> <ref>PMID:7849697</ref> <ref>PMID:7849721</ref> <ref>PMID:7809124</ref> <ref>PMID:7849006</ref> <ref>PMID:7711734</ref> <ref>PMID:7633420</ref> <ref>PMID:7633429</ref> <ref>PMID:8634718</ref> <ref>PMID:7627183</ref> <ref>PMID:7897635</ref> <ref>PMID:8723128</ref> <ref>PMID:8695804</ref> <ref>PMID:8834236</ref> <ref>PMID:9280283</ref> <ref>PMID:9260159</ref> <ref>PMID:9545398</ref> <ref>PMID:9445504</ref> <ref>PMID:10220140</ref> <ref>PMID:10678660</ref> <ref>PMID:10612838</ref> Defects in BTK may be the cause of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD) [MIM:[https://omim.org/entry/307200 307200]; also known as agammaglobulinemia and isolated growth hormone deficiency or Fleisher syndrome or isolated growth hormone deficiency type 3 (IGHD3). In rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD).
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/BTK_HUMAN BTK_HUMAN] Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis.<ref>PMID:9012831</ref> <ref>PMID:11606584</ref> <ref>PMID:16517732</ref> <ref>PMID:16738337</ref> <ref>PMID:16415872</ref> <ref>PMID:17932028</ref>
		+
		+	==See Also==
		+	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Brear P]]		[[Category: Brear P]]
	[[Category: Hyvonen M]]		[[Category: Hyvonen M]]
	[[Category: Wagstaff J]]		[[Category: Wagstaff J]]

OCA at 09:19, 12 May 2021

2021-05-12T09:19:18Z

←Older revision		Revision as of 09:19, 12 May 2021
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-	'''Unreleased structure'''

-	~~The entry 6yyg is ON HOLD until May 05 2022~~	+	==Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently bound to the PH domain of Bruton's tyrosine kinase mutant R28C==
-		+	<StructureSection load='6yyg' size='340' side='right'caption='[[6yyg]]' scene=''>
-	~~Authors: Brear, P., Wagstaff, J., Hyvonen, M.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YYG FirstGlance]. <br>
-	~~Description:~~ Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently bound to the PH domain of Bruton's tyrosine kinase mutant R28C	+	</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=6yyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yyg OCA], [https://pdbe.org/6yyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yyg RCSB], [https://www.ebi.ac.uk/pdbsum/6yyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yyg ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Wagstaff, J~~]]	+	__TOC__
-	[[Category: Hyvonen, M]]	+	</StructureSection>
-	[[Category: ~~Brear, P~~]]	+	[[Category: Large Structures]]
		+	[[Category: Brear P]]
		+	[[Category: Hyvonen M]]
		+	[[Category: Wagstaff J]]

OCA at 07:39, 22 July 2020

2020-07-22T07:39:10Z

←Older revision		Revision as of 07:39, 22 July 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6yyg is ON HOLD	+	The entry 6yyg is ON HOLD until May 05 2022

	Authors: Brear, P., Wagstaff, J., Hyvonen, M.		Authors: Brear, P., Wagstaff, J., Hyvonen, M.

OCA: Protected "6yyg" [edit=sysop:move=sysop]

2020-05-13T04:16:39Z

Protected "6yyg" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:16, 13 May 2020

OCA: New page: '''Unreleased structure''' The entry 6yyg is ON HOLD Authors: Brear, P., Wagstaff, J., Hyvonen, M. Description: Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently b...

2020-05-13T04:16:37Z

New page: '''Unreleased structure''' The entry 6yyg is ON HOLD Authors: Brear, P., Wagstaff, J., Hyvonen, M. Description: Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently b...

New page

'''Unreleased structure'''

The entry 6yyg is ON HOLD

Authors: Brear, P., Wagstaff, J., Hyvonen, M.

Description: Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently bound to the PH domain of Bruton's tyrosine kinase mutant R28C
[[Category: Unreleased Structures]]
[[Category: Wagstaff, J]]
[[Category: Hyvonen, M]]
[[Category: Brear, P]]

6yyg - Revision history

OCA at 13:38, 24 January 2024

OCA at 09:19, 12 May 2021

OCA at 07:39, 22 July 2020

OCA: Protected "6yyg" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6yyg is ON HOLD Authors: Brear, P., Wagstaff, J., Hyvonen, M. Description: Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently b...