4qt1 - Revision history

OCA at 15:09, 8 November 2023

OCA — Wed, 08 Nov 2023 15:09:39 GMT

←Older revision		Revision as of 15:09, 8 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qt1]] 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=4QT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QT1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qt1]] 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=4QT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QT1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</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]] 2.4Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</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=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [https://pdbe.org/4qt1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [https://www.ebi.ac.uk/pdbsum/4qt1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qt1 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=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [https://pdbe.org/4qt1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [https://www.ebi.ac.uk/pdbsum/4qt1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qt1 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 13:51, 22 February 2023

OCA — Wed, 22 Feb 2023 13:51:10 GMT

←Older revision		Revision as of 13:51, 22 February 2023
Line 3:		Line 3:
	<StructureSection load='4qt1' size='340' side='right'caption='[[4qt1]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='4qt1' size='340' side='right'caption='[[4qt1]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qt1]] 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=4QT1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QT1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qt1]] 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=4QT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QT1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [https://pdbe.org/4qt1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [https://www.ebi.ac.uk/pdbsum/4qt1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qt1 ProSAT]</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=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [~~http~~://pdbe.org/4qt1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qt1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qt1 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 24:		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: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific protein-tyrosine kinase]]~~	+	[[Category: Kuglstatter A]]
-	[[Category: Kuglstatter, A]]	+	[[Category: Shao A]]
-	[[Category: Shao, A]]	+
-	~~[[Category: Kinase-inhibitor complex]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 09:01, 24 April 2019

OCA — Wed, 24 Apr 2019 09:01:03 GMT

←Older revision		Revision as of 09:01, 24 April 2019
Line 1:		Line 1:

	==JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea==		==JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea==
-	<StructureSection load='4qt1' size='340' side='right' caption='[[4qt1]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='4qt1' size='340' side='right'caption='[[4qt1]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qt1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QT1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QT1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qt1]] 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=4QT1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QT1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</scene></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=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [http://pdbe.org/4qt1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [http://www.ebi.ac.uk/pdbsum/4qt1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qt1 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=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [http://pdbe.org/4qt1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [http://www.ebi.ac.uk/pdbsum/4qt1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qt1 ProSAT]</span></td></tr>
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 4qt1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4qt1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Janus kinase\|Janus kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[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 17:33, 9 March 2017

OCA — Thu, 09 Mar 2017 17:33:18 GMT

←Older revision		Revision as of 17:33, 9 March 2017
Line 1:		Line 1:
		+
	==JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea==		==JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea==
	<StructureSection load='4qt1' size='340' side='right' caption='[[4qt1]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='4qt1' size='340' side='right' caption='[[4qt1]], [[Resolution\|resolution]] 2.40Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [http://www.ebi.ac.uk/pdbsum/4qt1 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=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [http://pdbe.org/4qt1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [http://www.ebi.ac.uk/pdbsum/4qt1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qt1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 4qt1" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:54, 27 May 2015

OCA — Wed, 27 May 2015 15:54:31 GMT

←Older revision		Revision as of 15:54, 27 May 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea==
		+	<StructureSection load='4qt1' size='340' side='right' caption='[[4qt1]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4qt1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QT1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QT1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3C9:1-{(3S)-1-[(2-METHYLPROPYL)SULFONYL]PIPERIDIN-3-YL}-3-(5H-PYRROLO[2,3-B]PYRAZIN-2-YL)UREA'>3C9</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qt1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qt1 RCSB], [http://www.ebi.ac.uk/pdbsum/4qt1 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 discovery of a novel series of pyrrolopyrazines as JAK inhibitors with comparable enzyme and cellular activity to tofacitinib is described. The series was identified using a scaffold hopping approach aided by structure based drug design using principles of intramolecular hydrogen bonding for conformational restriction and targeting specific pockets for modulating kinase activity.

-	~~The entry 4qt1 is ON HOLD until Paper Publication~~	+	Scaffold hopping towards potent and selective JAK3 inhibitors: discovery of novel C-5 substituted pyrrolopyrazines.,de Vicente J, Lemoine R, Bartlett M, Hermann JC, Hekmat-Nejad M, Henningsen R, Jin S, Kuglstatter A, Li H, Lovey AJ, Menke J, Niu L, Patel V, Petersen A, Setti L, Shao A, Tivitmahaisoon P, Vu MD, Soth M Bioorg Med Chem Lett. 2014 Nov 1;24(21):4969-75. doi: 10.1016/j.bmcl.2014.09.031., Epub 2014 Sep 21. PMID:25262541<ref>PMID:25262541</ref>

-	~~Authors: Kuglstatter~~, A.~~, Shao, A~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Kuglstatter, A]]		[[Category: Kuglstatter, A]]
	[[Category: Shao, A]]		[[Category: Shao, A]]
		+	[[Category: Kinase-inhibitor complex]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 16:05, 24 December 2014

OCA — Wed, 24 Dec 2014 16:05:44 GMT

←Older revision		Revision as of 16:05, 24 December 2014
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	Description: JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea		Description: JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea
		+	[[Category: Unreleased Structures]]
		+	[[Category: Kuglstatter, A]]
		+	[[Category: Shao, A]]

OCA at 01:11, 7 August 2014

OCA — Thu, 07 Aug 2014 01:11:01 GMT

←Older revision		Revision as of 01:11, 7 August 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4qt1 is ON HOLD	+	The entry 4qt1 is ON HOLD until Paper Publication

-	Authors: Kuglstatter, A., Shao,A.	+	Authors: Kuglstatter, A., Shao, A.

	Description: JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea		Description: JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea

OCA: Protected "4qt1" [edit=sysop:move=sysop]

OCA — Wed, 16 Jul 2014 09:48:27 GMT

Protected "4qt1" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:48, 16 July 2014

OCA: New page: '''Unreleased structure''' The entry 4qt1 is ON HOLD Authors: Kuglstatter, A., Shao,A. Description: JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyr...

OCA — Wed, 16 Jul 2014 09:48:26 GMT

New page: '''Unreleased structure''' The entry 4qt1 is ON HOLD Authors: Kuglstatter, A., Shao,A. Description: JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyr...

New page

'''Unreleased structure'''

The entry 4qt1 is ON HOLD

Authors: Kuglstatter, A., Shao,A.

Description: JAK3 kinase domain in complex with 1-[(3S)-1-isobutylsulfonyl-3-piperidyl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)urea