5xyz - Revision history

OCA at 08:17, 22 November 2023

OCA — Wed, 22 Nov 2023 08:17:45 GMT

←Older revision		Revision as of 08:17, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='5xyz' size='340' side='right'caption='[[5xyz]], [[Resolution\|resolution]] 2.64Å' scene=''>		<StructureSection load='5xyz' size='340' side='right'caption='[[5xyz]], [[Resolution\|resolution]] 2.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xyz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XYZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5XYZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xyz]] 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=5XYZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XYZ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GYL:N~~-[~~3-(5-{~~[~~(2-chloro-6-fluorophenyl)methyl~~]~~amino}-1H-1,~~2~~,4-triazol-3-yl)phenyl]propanamide'>GYL</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]] 2.64Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Non~~-~~specific_protein~~-~~tyrosine_kinase Non~~-~~specific protein~~-~~tyrosine kinase~~], ~~with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2~~] </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GYL:N-[3-(5-{[(2-chloro-6-fluorophenyl)methyl]amino}-1H-1,2,4-triazol-3-yl)phenyl]propanamide'>GYL</scene></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=5xyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xyz OCA], [~~http~~://pdbe.org/5xyz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5xyz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5xyz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5xyz 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=5xyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xyz OCA], [https://pdbe.org/5xyz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xyz RCSB], [https://www.ebi.ac.uk/pdbsum/5xyz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xyz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/BTK_HUMAN BTK_HUMAN]] Defects in BTK are the cause of X-linked agammaglobulinemia (XLA) [MIM:[~~http~~://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:[~~http~~://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).	+	[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 ==		== Function ==
-	[~~[http~~://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>	+	[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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific protein-tyrosine kinase]]~~	+	[[Category: Cao R]]
-	[[Category: Cao, R]]	+	[[Category: Huang N]]
-	[[Category: Huang, N]]	+	[[Category: Li L]]
-	[[Category: Li, L]]	+	[[Category: Liu D]]
-	[[Category: Liu, D]]	+	[[Category: Qi XB]]
-	[[Category: Qi~~, X B~~]]	+	[[Category: Sun YZ]]
-	[[Category: Sun~~, Y Z~~]]	+	[[Category: Wang YL]]
-	[[Category: Wang~~, Y L~~]]	+	[[Category: Xie YT]]
-	[[Category: Xie~~, Y T]]~~	+
-	~~[[Category: Btk]]~~	+
-	~~[[Category: Covalent inhibitor]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:01, 14 October 2020

OCA — Wed, 14 Oct 2020 07:01:39 GMT

←Older revision		Revision as of 07:01, 14 October 2020
Line 1:		Line 1:

	==The structure of human BTK kinase domain in complex with a covalent inhibitor==		==The structure of human BTK kinase domain in complex with a covalent inhibitor==
-	<StructureSection load='5xyz' size='340' side='right' caption='[[5xyz]], [[Resolution\|resolution]] 2.64Å' scene=''>	+	<StructureSection load='5xyz' size='340' side='right'caption='[[5xyz]], [[Resolution\|resolution]] 2.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xyz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XYZ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5XYZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xyz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XYZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XYZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GYL:N-[3-(5-{[(2-chloro-6-fluorophenyl)methyl]amino}-1H-1,2,4-triazol-3-yl)phenyl]propanamide'>GYL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GYL:N-[3-(5-{[(2-chloro-6-fluorophenyl)methyl]amino}-1H-1,2,4-triazol-3-yl)phenyl]propanamide'>GYL</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5xyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xyz OCA], [http://pdbe.org/5xyz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xyz RCSB], [http://www.ebi.ac.uk/pdbsum/5xyz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xyz ProSAT]</span></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=5xyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xyz OCA], [http://pdbe.org/5xyz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xyz RCSB], [http://www.ebi.ac.uk/pdbsum/5xyz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xyz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5xyz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5xyz" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Cao, R]]		[[Category: Cao, R]]

OCA at 07:16, 23 May 2018

OCA — Wed, 23 May 2018 07:16:50 GMT

←Older revision		Revision as of 07:16, 23 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The ~~entry~~ 5xyz is ~~ON HOLD~~	+	==The structure of human BTK kinase domain in complex with a covalent inhibitor==
		+	<StructureSection load='5xyz' size='340' side='right' caption='[[5xyz]], [[Resolution\|resolution]] 2.64Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5xyz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XYZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XYZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GYL:N-[3-(5-{[(2-chloro-6-fluorophenyl)methyl]amino}-1H-1,2,4-triazol-3-yl)phenyl]propanamide'>GYL</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xyz OCA], [http://pdbe.org/5xyz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xyz RCSB], [http://www.ebi.ac.uk/pdbsum/5xyz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xyz ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/BTK_HUMAN BTK_HUMAN]] Defects in BTK are the cause of X-linked agammaglobulinemia (XLA) [MIM:[http://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:[http://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 ==
		+	[[http://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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	To explore novel kinase hinge-binding scaffolds, we carried out structure-based virtual screening against p38alpha MAPK as a model system. With the assistance of developed kinase-specific structural filters, we identify a novel lead compound that selectively inhibits a panel of kinases with threonine as the gatekeeper residue, including BTK and LCK. These kinases play important roles in lymphocyte activation, which encouraged us to design novel kinase inhibitors as drug candidates for ameliorating inflammatory diseases and cancers. Therefore, we chemically modified our substituted triazole-class lead compound to improve the binding affinity and selectivity via a "minimal decoration" strategy, which resulted in potent and selective kinase inhibitors against LCK (18 nM) and BTK (8 nM). Subsequent crystallographic experiments validated our design. These rationally designed compounds exhibit potent on-target inhibition against BTK in B cells or LCK in T cells, respectively. Our work demonstrates that structure-based virtual screening can be applied to facilitate the development of novel chemical entities in crowded chemical space in the field of kinase inhibitor discovery.

-	~~Authors:~~ Wang, Y~~.L.~~, Sun, Y~~.Z.~~, Cao, R., Liu, D., Xie, Y~~.T.~~, Li, L., Qi, X~~.B.~~, Huang, N.	+	In Silico Identification of a Novel Hinge-Binding Scaffold for Kinase Inhibitor Discovery.,Wang Y, Sun Y, Cao R, Liu D, Xie Y, Li L, Qi X, Huang N J Med Chem. 2017 Oct 26;60(20):8552-8564. doi: 10.1021/acs.jmedchem.7b01075. Epub, 2017 Oct 16. PMID:28945083<ref>PMID:28945083</ref>

-	~~Description: The structure of human BTK kinase domain in complex with~~ a ~~covalent inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5xyz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Cao, R]]		[[Category: Cao, R]]
	[[Category: Huang, N]]		[[Category: Huang, N]]
-	[[Category: Qi, X.B]]
	[[Category: Li, L]]		[[Category: Li, L]]
-	[[Category: Sun, Y.Z]]
-	[[Category: Wang, Y.L]]
-	[[Category: Xie, Y.T]]
	[[Category: Liu, D]]		[[Category: Liu, D]]
		+	[[Category: Qi, X B]]
		+	[[Category: Sun, Y Z]]
		+	[[Category: Wang, Y L]]
		+	[[Category: Xie, Y T]]
		+	[[Category: Btk]]
		+	[[Category: Covalent inhibitor]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 03:47, 16 May 2018

OCA — Wed, 16 May 2018 03:47:31 GMT

←Older revision		Revision as of 03:47, 16 May 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5xyz is ON HOLD ~~until Jul 11 2019~~	+	The entry 5xyz is ON HOLD

	Authors: Wang, Y.L., Sun, Y.Z., Cao, R., Liu, D., Xie, Y.T., Li, L., Qi, X.B., Huang, N.		Authors: Wang, Y.L., Sun, Y.Z., Cao, R., Liu, D., Xie, Y.T., Li, L., Qi, X.B., Huang, N.

OCA at 07:01, 10 January 2018

OCA — Wed, 10 Jan 2018 07:01:43 GMT

←Older revision		Revision as of 07:01, 10 January 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5xyz is ON HOLD	+	The entry 5xyz is ON HOLD until Jul 11 2019

	Authors: Wang, Y.L., Sun, Y.Z., Cao, R., Liu, D., Xie, Y.T., Li, L., Qi, X.B., Huang, N.		Authors: Wang, Y.L., Sun, Y.Z., Cao, R., Liu, D., Xie, Y.T., Li, L., Qi, X.B., Huang, N.
Line 7:		Line 7:
	Description: The structure of human BTK kinase domain in complex with a covalent inhibitor		Description: The structure of human BTK kinase domain in complex with a covalent inhibitor
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Huang, N]]
-	[[Category: Sun, Y.Z]]
-	[[Category: Wang, Y.L]]
	[[Category: Cao, R]]		[[Category: Cao, R]]
-	[[Category: ~~Liu~~, D]]	+	[[Category: Huang, N]]
	[[Category: Qi, X.B]]		[[Category: Qi, X.B]]
	[[Category: Li, L]]		[[Category: Li, L]]
		+	[[Category: Sun, Y.Z]]
		+	[[Category: Wang, Y.L]]
	[[Category: Xie, Y.T]]		[[Category: Xie, Y.T]]
		+	[[Category: Liu, D]]

OCA: Protected "5xyz" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 15:55:59 GMT

Protected "5xyz" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:55, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5xyz is ON HOLD Authors: Wang, Y.L., Sun, Y.Z., Cao, R., Liu, D., Xie, Y.T., Li, L., Qi, X.B., Huang, N. Description: The structure of human BTK ki...

OCA — Wed, 27 Sep 2017 15:55:57 GMT

New page: '''Unreleased structure''' The entry 5xyz is ON HOLD Authors: Wang, Y.L., Sun, Y.Z., Cao, R., Liu, D., Xie, Y.T., Li, L., Qi, X.B., Huang, N. Description: The structure of human BTK ki...

New page

'''Unreleased structure'''

The entry 5xyz is ON HOLD

Authors: Wang, Y.L., Sun, Y.Z., Cao, R., Liu, D., Xie, Y.T., Li, L., Qi, X.B., Huang, N.

Description: The structure of human BTK kinase domain in complex with a covalent inhibitor
[[Category: Unreleased Structures]]
[[Category: Huang, N]]
[[Category: Sun, Y.Z]]
[[Category: Wang, Y.L]]
[[Category: Cao, R]]
[[Category: Liu, D]]
[[Category: Qi, X.B]]
[[Category: Li, L]]
[[Category: Xie, Y.T]]