3piz - Revision history

OCA at 09:55, 6 September 2023

OCA — Wed, 06 Sep 2023 09:55:27 GMT

←Older revision		Revision as of 09:55, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3piz' size='340' side='right'caption='[[3piz]], [[Resolution\|resolution]] 2.21Å' scene=''>		<StructureSection load='3piz' size='340' side='right'caption='[[3piz]], [[Resolution\|resolution]] 2.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3piz]] is a 1 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=3PIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PIZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3piz]] is a 1 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=3PIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PIZ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=03C:[5-AMINO-1-(2-METHYLPHENYL)-1H-PYRAZOL-4-YL]{3~~-[~~1-(METHYLSULFONYL)PIPERIDIN-4-YL]PHENYL}METHANONE'>03C</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]] 2.21Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[~~[Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[3pix\|3pix]], [[3piy\|3piy]], [[3pj1\|3pj1]], [[3pj2\|3pj2]], [[3pj3\|3pj3]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=03C:[5-AMINO-1-(2-METHYLPHENYL)-1H-PYRAZOL-4-YL]{3-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]PHENYL}METHANONE'>03C</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>AGMX1, ATK, BPK, BTK ([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_protein~~-~~tyrosine_kinase Non~~-~~specific protein~~-~~tyrosine kinase~~]~~, with EC number~~ [~~https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3piz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3piz OCA], [https://pdbe.org/3piz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3piz RCSB], [https://www.ebi.ac.uk/pdbsum/3piz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3piz 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=3piz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3piz OCA], [https://pdbe.org/3piz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3piz RCSB], [https://www.ebi.ac.uk/pdbsum/3piz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3piz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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).	+	[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 ==
-	[[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>	+	[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 30:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific protein-tyrosine kinase]]~~	+	[[Category: Kuglstatter A]]
-	[[Category: Kuglstatter, A]]	+	[[Category: Wong A]]
-	[[Category: Wong, A]]	+
-	~~[[Category: Dfg-in]]~~	+
-	~~[[Category: Helix c-in]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-inhibitor complex~~]]	+

OCA at 08:41, 25 May 2022

OCA — Wed, 25 May 2022 08:41:31 GMT

←Older revision		Revision as of 08:41, 25 May 2022
Line 1:		Line 1:

	==Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone==		==Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone==
-	<StructureSection load='3piz' size='340' side='right' caption='[[3piz]], [[Resolution\|resolution]] 2.21Å' scene=''>	+	<StructureSection load='3piz' size='340' side='right'caption='[[3piz]], [[Resolution\|resolution]] 2.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3piz]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3PIZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3piz]] is a 1 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=3PIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PIZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=03C:[5-AMINO-1-(2-METHYLPHENYL)-1H-PYRAZOL-4-YL]{3-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]PHENYL}METHANONE'>03C</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=03C:[5-AMINO-1-(2-METHYLPHENYL)-1H-PYRAZOL-4-YL]{3-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]PHENYL}METHANONE'>03C</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3pix\|3pix]], [[3piy\|3piy]], [[3pj1\|3pj1]], [[3pj2\|3pj2]], [[3pj3\|3pj3]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3pix\|3pix]], [[3piy\|3piy]], [[3pj1\|3pj1]], [[3pj2\|3pj2]], [[3pj3\|3pj3]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AGMX1, ATK, BPK, BTK ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AGMX1, ATK, BPK, BTK ([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'>[~~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'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://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=3piz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3piz OCA], [~~http~~://pdbe.org/3piz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3piz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3piz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3piz 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=3piz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3piz OCA], [https://pdbe.org/3piz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3piz RCSB], [https://www.ebi.ac.uk/pdbsum/3piz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3piz 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 25:		Line 25:

	==See Also==		==See Also==
-	*[[Tyrosine kinase\|Tyrosine kinase]]	+	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 31:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Kuglstatter, A]]		[[Category: Kuglstatter, A]]

OCA at 15:51, 4 August 2016

OCA — Thu, 04 Aug 2016 15:51:56 GMT

←Older revision		Revision as of 15:51, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone==		==Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone==
	<StructureSection load='3piz' size='340' side='right' caption='[[3piz]], [[Resolution\|resolution]] 2.21Å' scene=''>		<StructureSection load='3piz' size='340' side='right' caption='[[3piz]], [[Resolution\|resolution]] 2.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3piz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PIZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3piz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PIZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=03C:[5-AMINO-1-(2-METHYLPHENYL)-1H-PYRAZOL-4-YL]{3-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]PHENYL}METHANONE'>03C</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=03C:[5-AMINO-1-(2-METHYLPHENYL)-1H-PYRAZOL-4-YL]{3-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]PHENYL}METHANONE'>03C</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3pix\|3pix]], [[3piy\|3piy]], [[3pj1\|3pj1]], [[3pj2\|3pj2]], [[3pj3\|3pj3]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3pix\|3pix]], [[3piy\|3piy]], [[3pj1\|3pj1]], [[3pj2\|3pj2]], [[3pj3\|3pj3]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AGMX1, ATK, BPK, BTK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AGMX1, ATK, BPK, BTK ([http://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'>[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=3piz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3piz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3piz RCSB], [http://www.ebi.ac.uk/pdbsum/3piz PDBsum]</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=3piz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3piz OCA], [http://pdbe.org/3piz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3piz RCSB], [http://www.ebi.ac.uk/pdbsum/3piz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3piz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3piz" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Kuglstatter, A]]		[[Category: Kuglstatter, A]]

OCA at 06:40, 19 December 2014

OCA — Fri, 19 Dec 2014 06:40:22 GMT

←Older revision		Revision as of 06:40, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3piz\| PDB=3piz \| SCENE= }}~~	+	==Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone==
-	===Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone===	+	<StructureSection load='3piz' size='340' side='right' caption='[[3piz]], [[Resolution\|resolution]] 2.21Å' scene=''>
-	{~~{ABSTRACT_PUBMED_21280133}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3piz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PIZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=03C:[5-AMINO-1-(2-METHYLPHENYL)-1H-PYRAZOL-4-YL]{3-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]PHENYL}METHANONE'>03C</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3pix\|3pix]], [[3piy\|3piy]], [[3pj1\|3pj1]], [[3pj2\|3pj2]], [[3pj3\|3pj3]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AGMX1, ATK, BPK, BTK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3piz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3piz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3piz RCSB], [http://www.ebi.ac.uk/pdbsum/3piz PDBsum]</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 ==
		+	Bruton's tyrosine kinase (BTK) plays a key role in B cell receptor signaling and is considered a promising drug target for lymphoma and inflammatory diseases. We have determined the X-ray crystal structures of BTK kinase domain in complex with six inhibitors from distinct chemical classes. Five different BTK protein conformations are stabilized by the bound inhibitors, providing insights into the structural flexibility of the Gly-rich loop, helix C, the DFG sequence, and activation loop. The conformational changes occur independent of activation loop phosphorylation and do not correlate with the structurally unchanged WEI motif in the Src homology 2-kinase domain linker. Two novel activation loop conformations and an atypical DFG conformation are observed representing unique inactive states of BTK. Two regions within the activation loop are shown to structurally transform between 3(10)- and alpha-helices, one of which collapses into the adenosine-5'-triphosphate binding pocket. The first crystal structure of a Tec kinase family member in the pharmacologically important DFG-out conformation and bound to a type II kinase inhibitor is described. The different protein conformations observed provide insights into the structural flexibility of BTK, the molecular basis of its regulation, and the structure-based design of specific inhibitors.

-	~~==Disease==~~	+	Insights into the conformational flexibility of Bruton's tyrosine kinase from multiple ligand complex structures.,Kuglstatter A, Wong A, Tsing S, Lee SW, Lou Y, Villasenor AG, Bradshaw JM, Shaw D, Barnett JW, Browner MF Protein Sci. 2011 Feb;20(2):428-36. doi: 10.1002/pro.575. PMID:21280133<ref>PMID:21280133</ref>
-	~~[[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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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>
-		+
-	~~==About this Structure==~~	+
-	[[3piz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA].	+

	==See Also==		==See Also==
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase\|Tyrosine kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:021280133</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
-	[[Category: Kuglstatter, A.]]	+	[[Category: Kuglstatter, A]]
-	[[Category: Wong, A.]]	+	[[Category: Wong, A]]
	[[Category: Dfg-in]]		[[Category: Dfg-in]]
	[[Category: Helix c-in]]		[[Category: Helix c-in]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transferase-inhibitor complex]]		[[Category: Transferase-inhibitor complex]]

OCA at 21:47, 24 March 2013

OCA — Sun, 24 Mar 2013 21:47:33 GMT

←Older revision		Revision as of 21:47, 24 March 2013
Line 1:		Line 1:
-	[[Image:3piz.png\|left\|200px]]
-
	{{STRUCTURE_3piz\| PDB=3piz \| SCENE= }}		{{STRUCTURE_3piz\| PDB=3piz \| SCENE= }}
-
	===Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone===		===Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone===
		+	{{ABSTRACT_PUBMED_21280133}}

-	~~{{ABSTRACT_PUBMED_21280133}}~~	+	==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>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021280133</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021280133</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 07:13, 20 October 2012

OCA — Sat, 20 Oct 2012 07:13:27 GMT

←Older revision		Revision as of 07:13, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3piz]] is a 1 chain structure ~~of [[Tyrosine kinase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA].	+	[[3piz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA].

	==See Also==		==See Also==

OCA at 15:38, 25 July 2012

OCA — Wed, 25 Jul 2012 15:38:41 GMT

←Older revision		Revision as of 15:38, 25 July 2012
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	[[Image:3piz.png\|left\|200px]]		[[Image:3piz.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3piz", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3piz\| PDB=3piz \| SCENE= }}		{{STRUCTURE_3piz\| PDB=3piz \| SCENE= }}

	===Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone===		===Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21280133}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21280133 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21280133}}		{{ABSTRACT_PUBMED_21280133}}

	==About this Structure==		==About this Structure==
-	[[3piz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA].	+	[[3piz]] is a 1 chain structure of [[Tyrosine kinase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA].
		+
		+	==See Also==
		+	*[[Tyrosine kinase\|Tyrosine kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~21280133~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021280133</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Kuglstatter, A.]]		[[Category: Kuglstatter, A.]]
	[[Category: Wong, A.]]		[[Category: Wong, A.]]
		+	[[Category: Dfg-in]]
		+	[[Category: Helix c-in]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-inhibitor complex]]

OCA at 06:36, 27 April 2011

OCA — Wed, 27 Apr 2011 06:36:33 GMT

←Older revision		Revision as of 06:36, 27 April 2011
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-	[[Image:3piz.~~jpg~~\|left\|200px]]	+	[[Image:3piz.png\|left\|200px]]

	<!--		<!--
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	<!--		<!--
-	The line below this paragraph, {{~~ABSTRACT_PUBMED_21171037~~}}, adds the Publication Abstract to the page	+	The line below this paragraph, {{ABSTRACT_PUBMED_21280133}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where ~~21171037~~ is the PubMed ID number.	+	(as it appears on PubMed at http://www.pubmed.gov), where 21280133 is the PubMed ID number.
	-->		-->
-	{{~~ABSTRACT_PUBMED_21171037~~}}	+	{{ABSTRACT_PUBMED_21280133}}

	==About this Structure==		==About this Structure==
Line 22:		Line 22:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~21171037~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:21280133</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Kuglstatter, A.]]		[[Category: Kuglstatter, A.]]
	[[Category: Wong, A.]]		[[Category: Wong, A.]]

OCA: Protected "3piz" [edit=sysop:move=sysop]

OCA — Wed, 12 Jan 2011 05:18:20 GMT

Protected "3piz" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:18, 12 January 2011

OCA at 05:18, 12 January 2011

OCA — Wed, 12 Jan 2011 05:18:18 GMT

←Older revision		Revision as of 05:18, 12 January 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:3piz.jpg\|left\|200px]]

-	The ~~entry 3piz~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3piz", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3piz\| PDB=3piz \| SCENE= }}

-	~~Authors: Kuglstatter, A., Wong, A.~~	+	===Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone===

-	Description: Crystal structure of BTK kinase domain complexed with (5-Amino-1-o-tolyl-1H-pyrazol-4-yl)-[3-(1-methanesulfonyl-piperidin-4-yl)-phenyl]-methanone

-	~~''Page seeded by~~ [http://oca.weizmann.ac.il/oca OCA ] ~~on Wed Dec 15 08~~:23:~~52 2010''~~	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21171037}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21171037 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21171037}}
		+
		+	==About this Structure==
		+	[[3piz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PIZ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:21171037</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific protein-tyrosine kinase]]
		+	[[Category: Kuglstatter, A.]]
		+	[[Category: Wong, A.]]