4hvg - Revision history

OCA at 15:11, 20 September 2023

OCA — Wed, 20 Sep 2023 15:11:39 GMT

←Older revision		Revision as of 15:11, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4hvg]] 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=4HVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HVG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4hvg]] 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=4HVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HVG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=19Q:2-CYCLOPROPYL-N-[(2S)-3-HYDROXY-3-METHYLBUTAN-2-YL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>19Q</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]] 2.75Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=19Q:2-CYCLOPROPYL-N-[(2S)-3-HYDROXY-3-METHYLBUTAN-2-YL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>19Q</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=4hvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvg OCA], [https://pdbe.org/4hvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hvg RCSB], [https://www.ebi.ac.uk/pdbsum/4hvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvg 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=4hvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvg OCA], [https://pdbe.org/4hvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hvg RCSB], [https://www.ebi.ac.uk/pdbsum/4hvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvg ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:18, 9 November 2022

OCA — Wed, 09 Nov 2022 08:18:13 GMT

←Older revision		Revision as of 08:18, 9 November 2022
Line 1:		Line 1:

	==JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide==		==JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide==
-	<StructureSection load='4hvg' size='340' side='right' caption='[[4hvg]], [[Resolution\|resolution]] 2.75Å' scene=''>	+	<StructureSection load='4hvg' size='340' side='right'caption='[[4hvg]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hvg]] 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=4HVG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4HVG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hvg]] 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=4HVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HVG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=19Q:2-CYCLOPROPYL-N-[(2S)-3-HYDROXY-3-METHYLBUTAN-2-YL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>19Q</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=19Q:2-CYCLOPROPYL-N-[(2S)-3-HYDROXY-3-METHYLBUTAN-2-YL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>19Q</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hvd\|4hvd]], [[4hvh\|4hvh]], [[4hvi\|4hvi]]</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=4hvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvg OCA], [https://pdbe.org/4hvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hvg RCSB], [https://www.ebi.ac.uk/pdbsum/4hvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvg ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JAK3 ([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=4hvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvg OCA], [~~http~~://pdbe.org/4hvg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4hvg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4hvg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvg ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Defects in JAK3 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:[~~http~~://omim.org/entry/600802 600802]]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.<ref>PMID:15121872</ref> <ref>PMID:18250158</ref> <ref>PMID:15831699</ref> [:]<ref>PMID:7659163</ref> <ref>PMID:9354668</ref> <ref>PMID:9753072</ref> <ref>PMID:10982185</ref> <ref>PMID:14615376</ref>	+	[https://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN] Defects in JAK3 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:[https://omim.org/entry/600802 600802]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.<ref>PMID:15121872</ref> <ref>PMID:18250158</ref> <ref>PMID:15831699</ref> [:]<ref>PMID:7659163</ref> <ref>PMID:9354668</ref> <ref>PMID:9753072</ref> <ref>PMID:10982185</ref> <ref>PMID:14615376</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.<ref>PMID:8022485</ref> <ref>PMID:7662955</ref> <ref>PMID:20440074</ref>	+	[https://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN] Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.<ref>PMID:8022485</ref> <ref>PMID:7662955</ref> <ref>PMID:20440074</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==See Also==		==See Also==
-	*[[Janus kinase\|Janus kinase]]	+	*[[Janus kinase 3D structures\|Janus 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: Kuglstatter, A]]	+	[[Category: Kuglstatter A]]
-	[[Category: Shao, A]]	+	[[Category: Shao A]]
-	~~[[Category: Kinase-inhibitor complex]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 17:16, 5 August 2016

OCA — Fri, 05 Aug 2016 17:16:50 GMT

←Older revision		Revision as of 17:16, 5 August 2016
Line 1:		Line 1:
		+
	==JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide==		==JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide==
	<StructureSection load='4hvg' size='340' side='right' caption='[[4hvg]], [[Resolution\|resolution]] 2.75Å' scene=''>		<StructureSection load='4hvg' size='340' side='right' caption='[[4hvg]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hvg]] 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=4HVG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hvg]] 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=4HVG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=19Q:2-CYCLOPROPYL-N-[(2S)-3-HYDROXY-3-METHYLBUTAN-2-YL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>19Q</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=19Q:2-CYCLOPROPYL-N-[(2S)-3-HYDROXY-3-METHYLBUTAN-2-YL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>19Q</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hvd\|4hvd]], [[4hvh\|4hvh]], [[4hvi\|4hvi]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hvd\|4hvd]], [[4hvh\|4hvh]], [[4hvi\|4hvi]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JAK3 ([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">JAK3 ([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=4hvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvg RCSB], [http://www.ebi.ac.uk/pdbsum/4hvg 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=4hvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvg OCA], [http://pdbe.org/4hvg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hvg RCSB], [http://www.ebi.ac.uk/pdbsum/4hvg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvg 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 4hvg" 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 12:26, 21 December 2014

OCA — Sun, 21 Dec 2014 12:26:33 GMT

←Older revision		Revision as of 12:26, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4hvg\| PDB=4hvg \| SCENE= }}~~	+	==JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide==
-	===JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide===	+	<StructureSection load='4hvg' size='340' side='right' caption='[[4hvg]], [[Resolution\|resolution]] 2.75Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23214979}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4hvg]] 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=4HVG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVG FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=19Q:2-CYCLOPROPYL-N-[(2S)-3-HYDROXY-3-METHYLBUTAN-2-YL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>19Q</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hvd\|4hvd]], [[4hvh\|4hvh]], [[4hvi\|4hvi]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JAK3 ([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=4hvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvg RCSB], [http://www.ebi.ac.uk/pdbsum/4hvg PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Defects in JAK3 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:[http://omim.org/entry/600802 600802]]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.<ref>PMID:15121872</ref> <ref>PMID:18250158</ref> <ref>PMID:15831699</ref> [:]<ref>PMID:7659163</ref> <ref>PMID:9354668</ref> <ref>PMID:9753072</ref> <ref>PMID:10982185</ref> <ref>PMID:14615376</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.<ref>PMID:8022485</ref> <ref>PMID:7662955</ref> <ref>PMID:20440074</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.

-	~~==Disease==~~	+	3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models.,Soth M, Hermann JC, Yee C, Alam M, Barnett JW, Berry P, Browner MF, Frank K, Frauchiger S, Harris S, He Y, Hekmat-Nejad M, Hendricks T, Henningsen R, Hilgenkamp R, Ho H, Hoffman A, Hsu PY, Hu DQ, Itano A, Jaime-Figueroa S, Jahangir A, Jin S, Kuglstatter A, Kutach AK, Liao C, Lynch S, Menke J, Niu L, Patel V, Railkar A, Roy D, Shao A, Shaw D, Steiner S, Sun Y, Tan SL, Wang S, Vu MD J Med Chem. 2013 Jan 10;56(1):345-56. doi: 10.1021/jm301646k. Epub 2012 Dec 19. PMID:23214979<ref>PMID:23214979</ref>
-	~~[[http://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Defects in JAK3 are a cause of severe combined immunodeficiency autosomal recessive T~~-~~cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM~~:~~[http://omim.org/entry/600802 600802]]. A form~~ of ~~severe combined immunodeficiency (SCID),~~ a ~~genetically~~ and ~~clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral~~ and ~~cell-mediated immunity~~, ~~leukopenia~~, ~~and low or absent antibody levels. Patients present in infancy recurrent~~, ~~persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T~~-~~cell-mediated cellular immunity due to a defect in~~ T-~~cell development~~.~~<ref>PMID~~:~~15121872</ref><ref>PMID~~:~~18250158<~~/~~ref><ref>~~PMID:~~15831699</ref>[:]<ref>PMID:7659163</ref><ref>PMID:9354668</ref><ref>PMID:9753072</ref><ref>PMID:10982185</ref>~~<ref>PMID:~~14615376~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http://www.uniprot.org/uniprot~~/~~JAK3_HUMAN JAK3_HUMAN]] Non-receptor tyrosine kinase involved in various processes such as cell growth~~, ~~development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays~~ a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the ~~receptor, creating docking sites for STATs proteins~~. ~~Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor~~. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.<~~ref~~>~~PMID:8022485</ref><ref>PMID:7662955</ref><ref>PMID:20440074~~</~~ref~~>	+	</div>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~4hvg~~]] 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=4HVG OCA].	+	*[[Janus kinase\|Janus kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<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: Shao, A.]]	+	[[Category: Shao, A]]
	[[Category: Kinase-inhibitor complex]]		[[Category: Kinase-inhibitor complex]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 02:18, 25 March 2013

OCA — Mon, 25 Mar 2013 02:18:36 GMT

←Older revision		Revision as of 02:18, 25 March 2013
Line 1:		Line 1:
-	[[Image:4hvg.png\|left\|200px]]
-
	{{STRUCTURE_4hvg\| PDB=4hvg \| SCENE= }}		{{STRUCTURE_4hvg\| PDB=4hvg \| SCENE= }}
-
	===JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide===		===JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide===
-
	{{ABSTRACT_PUBMED_23214979}}		{{ABSTRACT_PUBMED_23214979}}
		+
		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Defects in JAK3 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:[http://omim.org/entry/600802 600802]]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.<ref>PMID:15121872</ref><ref>PMID:18250158</ref><ref>PMID:15831699</ref>[:]<ref>PMID:7659163</ref><ref>PMID:9354668</ref><ref>PMID:9753072</ref><ref>PMID:10982185</ref><ref>PMID:14615376</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.<ref>PMID:8022485</ref><ref>PMID:7662955</ref><ref>PMID:20440074</ref>

	==About this Structure==		==About this Structure==
	[[4hvg]] 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=4HVG OCA].		[[4hvg]] 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=4HVG OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 12:51, 30 January 2013

OCA — Wed, 30 Jan 2013 12:51:38 GMT

←Older revision		Revision as of 12:51, 30 January 2013
Line 1:		Line 1:
-	[[Image:4hvg.~~jpg~~\|left\|200px]]	+	[[Image:4hvg.png\|left\|200px]]

	{{STRUCTURE_4hvg\| PDB=4hvg \| SCENE= }}		{{STRUCTURE_4hvg\| PDB=4hvg \| SCENE= }}

OCA at 08:54, 16 January 2013

OCA — Wed, 16 Jan 2013 08:54:06 GMT

←Older revision		Revision as of 08:54, 16 January 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4hvg.jpg\|left\|200px]]

-	~~The entry~~ 4hvg ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4hvg\| PDB=4hvg \| SCENE= }}

-	~~Authors: Kuglstatter~~, A., ~~Shao, A.~~	+	===JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide===

-	~~Description~~:	+	{{ABSTRACT_PUBMED_23214979}}
		+
		+	==About this Structure==
		+	[[4hvg]] 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=4HVG OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific protein-tyrosine kinase]]
		+	[[Category: Kuglstatter, A.]]
		+	[[Category: Shao, A.]]
		+	[[Category: Kinase-inhibitor complex]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:07, 21 November 2012

OCA — Wed, 21 Nov 2012 09:07:44 GMT

←Older revision		Revision as of 09:07, 21 November 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4hvg is ON HOLD	+	The entry 4hvg is ON HOLD until Paper Publication

	Authors: Kuglstatter, A., Shao, A.		Authors: Kuglstatter, A., Shao, A.

-	Description: ~~JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide~~	+	Description:

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

OCA — Wed, 14 Nov 2012 06:20:04 GMT

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

←Older revision

Revision as of 06:20, 14 November 2012

OCA: New page: '''Unreleased structure''' The entry 4hvg is ON HOLD Authors: Kuglstatter, A., Shao, A. Description: JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carbox...

OCA — Wed, 14 Nov 2012 06:20:03 GMT

New page: '''Unreleased structure''' The entry 4hvg is ON HOLD Authors: Kuglstatter, A., Shao, A. Description: JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carbox...

New page

'''Unreleased structure'''

The entry 4hvg is ON HOLD

Authors: Kuglstatter, A., Shao, A.

Description: JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide