4ppa - Revision history

OCA at 17:20, 20 September 2023

OCA — Wed, 20 Sep 2023 17:20:09 GMT

←Older revision		Revision as of 17:20, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ppa]] 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=4PPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPA FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ppa]] 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=4PPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</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]] 2.67Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [https://pdbe.org/4ppa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [https://www.ebi.ac.uk/pdbsum/4ppa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppa 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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [https://pdbe.org/4ppa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [https://www.ebi.ac.uk/pdbsum/4ppa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppa ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:22, 8 February 2023

OCA — Wed, 08 Feb 2023 07:22:34 GMT

←Older revision		Revision as of 07:22, 8 February 2023
Line 1:		Line 1:

	==ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)==		==ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)==
-	<StructureSection load='4ppa' size='340' side='right' caption='[[4ppa]], [[Resolution\|resolution]] 2.67Å' scene=''>	+	<StructureSection load='4ppa' size='340' side='right'caption='[[4ppa]], [[Resolution\|resolution]] 2.67Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ppa]] is a 2 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=4PPA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4PPA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ppa]] 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=4PPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4pp9\|4pp9]], [[4ppb\|4ppb]], [[4ppc\|4ppc]]</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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [https://pdbe.org/4ppa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [https://www.ebi.ac.uk/pdbsum/4ppa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppa ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITK, EMT, LYK ([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='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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [~~http~~://pdbe.org/4ppa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ppa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppa ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN]] Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:[~~http~~://omim.org/entry/613011 613011]]. LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.<ref>PMID:19425169</ref>	+	[https://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN] Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:[https://omim.org/entry/613011 613011]. LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.<ref>PMID:19425169</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN]] Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation.<ref>PMID:12186560</ref> <ref>PMID:12682224</ref> <ref>PMID:21725281</ref>	+	[https://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN] Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation.<ref>PMID:12186560</ref> <ref>PMID:12682224</ref> <ref>PMID:21725281</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4ppa" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ppa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific protein-tyrosine kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Eigenbrot, C]]	+	[[Category: Eigenbrot C]]
-	[[Category: Shia, S]]	+	[[Category: Shia S]]
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 06:49, 31 January 2018

OCA — Wed, 31 Jan 2018 06:49:26 GMT

←Older revision		Revision as of 06:49, 31 January 2018
Line 3:		Line 3:
	<StructureSection load='4ppa' size='340' side='right' caption='[[4ppa]], [[Resolution\|resolution]] 2.67Å' scene=''>		<StructureSection load='4ppa' size='340' side='right' caption='[[4ppa]], [[Resolution\|resolution]] 2.67Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ppa]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ppa]] is a 2 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=4PPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4pp9\|4pp9]], [[4ppb\|4ppb]], [[4ppc\|4ppc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4pp9\|4pp9]], [[4ppb\|4ppb]], [[4ppc\|4ppc]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITK, EMT, LYK ([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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [http://pdbe.org/4ppa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [http://www.ebi.ac.uk/pdbsum/4ppa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppa ProSAT]</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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [http://pdbe.org/4ppa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [http://www.ebi.ac.uk/pdbsum/4ppa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppa ProSAT]</span></td></tr>
Line 22:		Line 23:
	</div>		</div>
	<div class="pdbe-citations 4ppa" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ppa" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Tyrosine kinase\|Tyrosine kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Eigenbrot, C]]		[[Category: Eigenbrot, C]]

OCA at 11:03, 11 August 2016

OCA — Thu, 11 Aug 2016 11:03:58 GMT

←Older revision		Revision as of 11:03, 11 August 2016
Line 1:		Line 1:
		+
	==ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)==		==ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)==
	<StructureSection load='4ppa' size='340' side='right' caption='[[4ppa]], [[Resolution\|resolution]] 2.67Å' scene=''>		<StructureSection load='4ppa' size='340' side='right' caption='[[4ppa]], [[Resolution\|resolution]] 2.67Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4pp9\|4pp9]], [[4ppb\|4ppb]], [[4ppc\|4ppc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4pp9\|4pp9]], [[4ppb\|4ppb]], [[4ppc\|4ppc]]</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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [http://www.ebi.ac.uk/pdbsum/4ppa 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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [http://pdbe.org/4ppa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [http://www.ebi.ac.uk/pdbsum/4ppa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppa ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 4ppa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine kinase\|Tyrosine kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:49, 5 January 2015

OCA — Mon, 05 Jan 2015 08:49:41 GMT

←Older revision		Revision as of 08:49, 5 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ppa]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPA FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ppa]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPA FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4pp9\|4pp9]], [[4ppb\|4ppb]], [[4ppc\|4ppc]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4pp9\|4pp9]], [[4ppb\|4ppb]], [[4ppc\|4ppc]]</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [http://www.ebi.ac.uk/pdbsum/4ppa 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=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [http://www.ebi.ac.uk/pdbsum/4ppa PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN]] Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:[http://omim.org/entry/613011 613011]]. LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.<ref>PMID:19425169</ref>		[[http://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN]] Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:[http://omim.org/entry/613011 613011]]. LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.<ref>PMID:19425169</ref>
Line 18:		Line 18:
	Discovery and optimization of indazoles as potent and selective interleukin-2 inducible T cell kinase (ITK) inhibitors.,Pastor RM, Burch JD, Magnuson S, Ortwine DF, Chen Y, De La Torre K, Ding X, Eigenbrot C, Johnson A, Liimatta M, Liu Y, Shia S, Wang X, Wu LC, Pei Z Bioorg Med Chem Lett. 2014 Jun 1;24(11):2448-52. doi: 10.1016/j.bmcl.2014.04.023., Epub 2014 Apr 16. PMID:24767842<ref>PMID:24767842</ref>		Discovery and optimization of indazoles as potent and selective interleukin-2 inducible T cell kinase (ITK) inhibitors.,Pastor RM, Burch JD, Magnuson S, Ortwine DF, Chen Y, De La Torre K, Ding X, Eigenbrot C, Johnson A, Liimatta M, Liu Y, Shia S, Wang X, Wu LC, Pei Z Bioorg Med Chem Lett. 2014 Jun 1;24(11):2448-52. doi: 10.1016/j.bmcl.2014.04.023., Epub 2014 Apr 16. PMID:24767842<ref>PMID:24767842</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
	== References ==		== References ==
Line 25:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
-	[[Category: Eigenbrot, C.]]	+	[[Category: Eigenbrot, C]]
-	[[Category: Shia, S.]]	+	[[Category: Shia, S]]
	[[Category: Protein kinase]]		[[Category: Protein kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:07, 4 June 2014

OCA — Wed, 04 Jun 2014 05:07:54 GMT

←Older revision		Revision as of 05:07, 4 June 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)==
		+	<StructureSection load='4ppa' size='340' side='right' caption='[[4ppa]], [[Resolution\|resolution]] 2.67Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ppa]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPA FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VU:N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VU</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4pp9\|4pp9]], [[4ppb\|4ppb]], [[4ppc\|4ppc]]</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ppa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ppa RCSB], [http://www.ebi.ac.uk/pdbsum/4ppa PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN]] Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:[http://omim.org/entry/613011 613011]]. LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.<ref>PMID:19425169</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN]] Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation.<ref>PMID:12186560</ref> <ref>PMID:12682224</ref> <ref>PMID:21725281</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	There is evidence that small molecule inhibitors of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signaling cascade, could represent a novel asthma therapeutic class. Moreover, given the expected chronic dosing regimen of any asthma treatment, highly selective as well as potent inhibitors would be strongly preferred in any potential therapeutic. Here we report hit-to-lead optimization of a series of indazoles that demonstrate sub-nanomolar inhibitory potency against ITK with strong cellular activity and good kinase selectivity. We also elucidate the binding mode of these inhibitors by solving the X-ray crystal structures of the complexes.

-	~~The entry 4ppa is ON HOLD until Paper Publication~~	+	Discovery and optimization of indazoles as potent and selective interleukin-2 inducible T cell kinase (ITK) inhibitors.,Pastor RM, Burch JD, Magnuson S, Ortwine DF, Chen Y, De La Torre K, Ding X, Eigenbrot C, Johnson A, Liimatta M, Liu Y, Shia S, Wang X, Wu LC, Pei Z Bioorg Med Chem Lett. 2014 Jun 1;24(11):2448-52. doi: 10.1016/j.bmcl.2014.04.023., Epub 2014 Apr 16. PMID:24767842<ref>PMID:24767842</ref>

-	~~Authors~~: Eigenbrot, C., Shia, S.	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~ITK~~ kinase ~~domain with compound 11 (N-~~[~~1-(3-CYANOBENZYL)-1H~~-~~PYRAZOL-4-YL~~]~~-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific protein-tyrosine kinase]]
		+	[[Category: Eigenbrot, C.]]
		+	[[Category: Shia, S.]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "4ppa" [edit=sysop:move=sysop]

OCA — Wed, 12 Mar 2014 12:33:33 GMT

Protected "4ppa" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:33, 12 March 2014

OCA: New page: '''Unreleased structure''' The entry 4ppa is ON HOLD until Paper Publication Authors: Eigenbrot, C., Shia, S. Description: ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-P...

OCA — Wed, 12 Mar 2014 12:33:32 GMT

New page: '''Unreleased structure''' The entry 4ppa is ON HOLD until Paper Publication Authors: Eigenbrot, C., Shia, S. Description: ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-P...

New page

'''Unreleased structure'''

The entry 4ppa is ON HOLD until Paper Publication

Authors: Eigenbrot, C., Shia, S.

Description: ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)