3zep - Revision history

OCA at 05:44, 10 August 2022

OCA — Wed, 10 Aug 2022 05:44:16 GMT

←Older revision		Revision as of 05:44, 10 August 2022
Line 1:		Line 1:

	==Crystal Structure of JAK3 Kinase Domain in Complex with a Pyrrolopyrazine-2-phenyl Ether Inhibitor==		==Crystal Structure of JAK3 Kinase Domain in Complex with a Pyrrolopyrazine-2-phenyl Ether Inhibitor==
-	<StructureSection load='3zep' size='340' side='right' caption='[[3zep]], [[Resolution\|resolution]] 2.35Å' scene=''>	+	<StructureSection load='3zep' size='340' side='right'caption='[[3zep]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zep]] is a 4 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=3ZEP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3ZEP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zep]] is a 4 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=3ZEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZEP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1NX:2-[[(3R)-3-ACETAMIDO-2,3-DIHYDRO-1H-INDEN-5-YL]OXY]-N-[(1S)-1-CYCLOPROPYLETHYL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>1NX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1NX:2-[[(3R)-3-ACETAMIDO-2,3-DIHYDRO-1H-INDEN-5-YL]OXY]-N-[(1S)-1-CYCLOPROPYLETHYL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>1NX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=3zep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zep OCA], [~~http~~://pdbe.org/3zep PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3zep RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3zep PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3zep 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=3zep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zep OCA], [https://pdbe.org/3zep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zep RCSB], [https://www.ebi.ac.uk/pdbsum/3zep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zep 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 23:		Line 23:

	==See Also==		==See Also==
-	*[[Janus kinase\|Janus kinase]]	+	*[[Janus kinase 3D structures\|Janus kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Blaesse, M]]		[[Category: Blaesse, M]]
	[[Category: Boettcher, J]]		[[Category: Boettcher, J]]

OCA at 14:10, 4 August 2016

OCA — Thu, 04 Aug 2016 14:10:19 GMT

←Older revision		Revision as of 14:10, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of JAK3 Kinase Domain in Complex with a Pyrrolopyrazine-2-phenyl Ether Inhibitor==		==Crystal Structure of JAK3 Kinase Domain in Complex with a Pyrrolopyrazine-2-phenyl Ether Inhibitor==
	<StructureSection load='3zep' size='340' side='right' caption='[[3zep]], [[Resolution\|resolution]] 2.35Å' scene=''>		<StructureSection load='3zep' size='340' side='right' caption='[[3zep]], [[Resolution\|resolution]] 2.35Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1NX:2-[[(3R)-3-ACETAMIDO-2,3-DIHYDRO-1H-INDEN-5-YL]OXY]-N-[(1S)-1-CYCLOPROPYLETHYL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>1NX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1NX:2-[[(3R)-3-ACETAMIDO-2,3-DIHYDRO-1H-INDEN-5-YL]OXY]-N-[(1S)-1-CYCLOPROPYLETHYL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>1NX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=3zep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zep OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zep RCSB], [http://www.ebi.ac.uk/pdbsum/3zep 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=3zep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zep OCA], [http://pdbe.org/3zep PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zep RCSB], [http://www.ebi.ac.uk/pdbsum/3zep PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zep 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 3zep" style="background-color:#fffaf0;"></div>

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

OCA at 18:38, 21 December 2014

OCA — Sun, 21 Dec 2014 18:38:20 GMT

←Older revision		Revision as of 18:38, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3zep\| PDB=3zep \| SCENE= }}~~	+	==Crystal Structure of JAK3 Kinase Domain in Complex with a Pyrrolopyrazine-2-phenyl Ether Inhibitor==
-	===Crystal Structure of JAK3 Kinase Domain in Complex with a Pyrrolopyrazine-2-phenyl Ether Inhibitor===	+	<StructureSection load='3zep' size='340' side='right' caption='[[3zep]], [[Resolution\|resolution]] 2.35Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23541670}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3zep]] is a 4 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=3ZEP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZEP FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1NX:2-[[(3R)-3-ACETAMIDO-2,3-DIHYDRO-1H-INDEN-5-YL]OXY]-N-[(1S)-1-CYCLOPROPYLETHYL]-5H-PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE'>1NX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=3zep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zep OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zep RCSB], [http://www.ebi.ac.uk/pdbsum/3zep 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>		[[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 ==
		+	We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity. Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity.

-	~~==Function==~~	+	Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors.,Jaime-Figueroa S, De Vicente J, Hermann J, Jahangir A, Jin S, Kuglstatter A, Lynch SM, Menke J, Niu L, Patel V, Shao A, Soth M, Vu MD, Yee C Bioorg Med Chem Lett. 2013 May 1;23(9):2522-6. doi: 10.1016/j.bmcl.2013.03.015., Epub 2013 Mar 14. PMID:23541670<ref>PMID:23541670</ref>
-	[~~[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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3zep]] is~~ a ~~4 chain structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=3ZEP OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023541670</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Janus kinase\|Janus kinase]]
-	[[Category: Blaesse, M.]]	+	== References ==
-	[[Category: Boettcher, J.]]	+	<references/>
-	[[Category: Jestel, A.]]	+	__TOC__
-	[[Category: Kuglstatter, A.]]	+	</StructureSection>
-	[[Category: Nagel, S.]]	+	[[Category: Human]]
		+	[[Category: Blaesse, M]]
		+	[[Category: Boettcher, J]]
		+	[[Category: Jestel, A]]
		+	[[Category: Kuglstatter, A]]
		+	[[Category: Nagel, S]]
	[[Category: Atp site kinase inhibitor]]		[[Category: Atp site kinase inhibitor]]
	[[Category: Cancer]]		[[Category: Cancer]]

OCA at 13:39, 11 December 2013

OCA — Wed, 11 Dec 2013 13:39:51 GMT

←Older revision		Revision as of 13:39, 11 December 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_3zep\| PDB=3zep \| SCENE= }}
		+	===Crystal Structure of JAK3 Kinase Domain in Complex with a Pyrrolopyrazine-2-phenyl Ether Inhibitor===
		+	{{ABSTRACT_PUBMED_23541670}}

-	~~The~~ entry ~~3zep~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==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>

-	~~Authors~~: ~~Kuglstatter~~, A., ~~Jestel~~, A., ~~Nagel~~, S., ~~Boettcher~~, J., ~~Blaesse~~, M.	+	==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>

-	~~Description~~: ~~Pyrrolopyrazine~~-2-~~phenyl ether~~	+	==About this Structure==
		+	[[3zep]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZEP OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023541670</ref><references group="xtra"/><references/>
		+	[[Category: Blaesse, M.]]
		+	[[Category: Boettcher, J.]]
		+	[[Category: Jestel, A.]]
		+	[[Category: Kuglstatter, A.]]
		+	[[Category: Nagel, S.]]
		+	[[Category: Atp site kinase inhibitor]]
		+	[[Category: Cancer]]
		+	[[Category: Common-gamma chain]]
		+	[[Category: Interleukin-2]]
		+	[[Category: Scid]]
		+	[[Category: Severe combined immunodeficiency]]
		+	[[Category: Stat5]]
		+	[[Category: Stat6]]
		+	[[Category: Transferase]]

OCA at 08:37, 2 January 2013

OCA — Wed, 02 Jan 2013 08:37:59 GMT

←Older revision		Revision as of 08:37, 2 January 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3zep is ON HOLD	+	The entry 3zep is ON HOLD until Paper Publication

	Authors: Kuglstatter, A., Jestel, A., Nagel, S., Boettcher, J., Blaesse, M.		Authors: Kuglstatter, A., Jestel, A., Nagel, S., Boettcher, J., Blaesse, M.

	Description: Pyrrolopyrazine-2-phenyl ether		Description: Pyrrolopyrazine-2-phenyl ether

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

OCA — Wed, 12 Dec 2012 20:36:02 GMT

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

←Older revision

Revision as of 20:36, 12 December 2012

OCA: New page: '''Unreleased structure''' The entry 3zep is ON HOLD Authors: Kuglstatter, A., Jestel, A., Nagel, S., Boettcher, J., Blaesse, M. Description: Pyrrolopyrazine-2-phenyl ether

OCA — Wed, 12 Dec 2012 20:36:01 GMT

New page: '''Unreleased structure''' The entry 3zep is ON HOLD Authors: Kuglstatter, A., Jestel, A., Nagel, S., Boettcher, J., Blaesse, M. Description: Pyrrolopyrazine-2-phenyl ether

New page

'''Unreleased structure'''

The entry 3zep is ON HOLD

Authors: Kuglstatter, A., Jestel, A., Nagel, S., Boettcher, J., Blaesse, M.

Description: Pyrrolopyrazine-2-phenyl ether