6nzf - Revision history

OCA at 07:01, 11 October 2023

OCA — Wed, 11 Oct 2023 07:01:59 GMT

←Older revision		Revision as of 07:01, 11 October 2023
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	<StructureSection load='6nzf' size='340' side='right'caption='[[6nzf]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='6nzf' size='340' side='right'caption='[[6nzf]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nzf]] 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=6NZF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NZF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nzf]] 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=6NZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NZF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L91:6-[(5-fluoropyridin-2-yl)amino]-N-methyl-4-{[2-(methylsulfonyl)phenyl]amino}pyridine-3-carboxamide'>L91</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.39Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TYK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L91:6-[(5-fluoropyridin-2-yl)amino]-N-methyl-4-{[2-(methylsulfonyl)phenyl]amino}pyridine-3-carboxamide'>L91</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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'>[https://proteopedia.org/fgij/fg.htm?mol=6nzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nzf OCA], [https://pdbe.org/6nzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nzf RCSB], [https://www.ebi.ac.uk/pdbsum/6nzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nzf 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=6nzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nzf OCA], [~~http~~://pdbe.org/6nzf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nzf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nzf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nzf ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN]] Mendelian susceptibility to mycobacterial diseases;Autosomal recessive hyper IgE syndrome. Defects in TYK2 are the cause of protein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:[~~http~~://omim.org/entry/611521 611521]]; also known as autosomal recessive hyper-IgE syndrome (HIES) with atypical mycobacteriosis. TYK2 deficiency consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.	+	[https://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN] Mendelian susceptibility to mycobacterial diseases;Autosomal recessive hyper IgE syndrome. Defects in TYK2 are the cause of protein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:[https://omim.org/entry/611521 611521]; also known as autosomal recessive hyper-IgE syndrome (HIES) with atypical mycobacteriosis. TYK2 deficiency consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN]] Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.<ref>PMID:7526154</ref>	+	[https://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN] Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.<ref>PMID:7526154</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6nzf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6nzf" 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: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific protein-tyrosine kinase]]~~	+	[[Category: Muckelbauer JM]]
-	[[Category: Muckelbauer~~, J M]]~~	+
-	~~[[Category: Jtk1]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:28, 6 November 2019

OCA — Wed, 06 Nov 2019 08:28:31 GMT

←Older revision		Revision as of 08:28, 6 November 2019
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	<StructureSection load='6nzf' size='340' side='right'caption='[[6nzf]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='6nzf' size='340' side='right'caption='[[6nzf]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nzf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NZF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nzf]] 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=6NZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NZF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L91:6-[(5-fluoropyridin-2-yl)amino]-N-methyl-4-{[2-(methylsulfonyl)phenyl]amino}pyridine-3-carboxamide'>L91</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L91:6-[(5-fluoropyridin-2-yl)amino]-N-methyl-4-{[2-(methylsulfonyl)phenyl]amino}pyridine-3-carboxamide'>L91</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TYK2 ([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=6nzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nzf OCA], [http://pdbe.org/6nzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nzf RCSB], [http://www.ebi.ac.uk/pdbsum/6nzf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nzf 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=6nzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nzf OCA], [http://pdbe.org/6nzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nzf RCSB], [http://www.ebi.ac.uk/pdbsum/6nzf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nzf ProSAT]</span></td></tr>
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 06:18, 24 July 2019

OCA — Wed, 24 Jul 2019 06:18:03 GMT

←Older revision		Revision as of 06:18, 24 July 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nzf is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH Compound_5 AKA 4-[(2-CARBAMOYLPHEN YL)AMINO]-6-[(5-FLUOROPYRIDIN-2-YL)AMINO]-N-METHYLPYRIDINE -3-CARBOXAMIDE==
		+	<StructureSection load='6nzf' size='340' side='right'caption='[[6nzf]], [[Resolution\|resolution]] 2.39Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6nzf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NZF FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L91:6-[(5-fluoropyridin-2-yl)amino]-N-methyl-4-{[2-(methylsulfonyl)phenyl]amino}pyridine-3-carboxamide'>L91</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6nzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nzf OCA], [http://pdbe.org/6nzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nzf RCSB], [http://www.ebi.ac.uk/pdbsum/6nzf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nzf ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN]] Mendelian susceptibility to mycobacterial diseases;Autosomal recessive hyper IgE syndrome. Defects in TYK2 are the cause of protein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:[http://omim.org/entry/611521 611521]]; also known as autosomal recessive hyper-IgE syndrome (HIES) with atypical mycobacteriosis. TYK2 deficiency consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN]] Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.<ref>PMID:7526154</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	As a member of the Janus (JAK) family of nonreceptor tyrosine kinases, TYK2 plays an important role in mediating the signaling of pro-inflammatory cytokines including IL-12, IL-23, and type 1 interferons. The nicotinamide 4, identified by a SPA-based high-throughput screen targeting the TYK2 pseudokinase domain, potently inhibits IL-23 and IFNalpha signaling in cellular assays. The described work details the optimization of this poorly selective hit (4) to potent and selective molecules such as 47 and 48. The discoveries described herein were critical to the eventual identification of the clinical TYK2 JH2 inhibitor (see following report in this issue). Compound 48 provided robust inhibition in a mouse IL-12-induced IFNgamma pharmacodynamic model as well as efficacy in an IL-23 and IL-12-dependent mouse colitis model. These results demonstrate the ability of TYK2 JH2 domain binders to provide a highly selective alternative to conventional TYK2 orthosteric inhibitors.

-	~~Authors:~~ Muckelbauer, J.M.	+	Identification of N-Methyl Nicotinamide and N-Methyl Pyridazine-3-Carboxamide Pseudokinase Domain Ligands as Highly Selective Allosteric Inhibitors of Tyrosine Kinase 2 (TYK2).,Moslin R, Zhang Y, Wrobleski ST, Lin S, Mertzman M, Spergel S, Tokarski JS, Strnad J, Gillooly K, McIntyre KW, Zupa-Fernandez A, Cheng L, Sun H, Chaudhry C, Huang C, D'Arienzo C, Heimrich E, Yang X, Muckelbauer JK, Chang C, Tredup J, Mulligan D, Xie D, Aranibar N, Chiney M, Burke JR, Lombardo L, Carter PH, Weinstein DS J Med Chem. 2019 Jul 17. doi: 10.1021/acs.jmedchem.9b00443. PMID:31314518<ref>PMID:31314518</ref>

-	~~Description: CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH Compound_5 AKA 4~~-~~[(2-CARBAMOYLPHEN YL)AMINO]-6~~-[~~(5-FLUOROPYRIDIN-2-YL)AMINO~~]~~-N-METHYLPYRIDINE -3-CARBOXAMIDE~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Muckelbauer, J.M]]	+	<div class="pdbe-citations 6nzf" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Non-specific protein-tyrosine kinase]]
		+	[[Category: Muckelbauer, J M]]
		+	[[Category: Jtk1]]
		+	[[Category: Transferase]]

OCA at 04:56, 27 March 2019

OCA — Wed, 27 Mar 2019 04:56:43 GMT

←Older revision		Revision as of 04:56, 27 March 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6nzf is ON HOLD	+	The entry 6nzf is ON HOLD until Paper Publication

	Authors: Muckelbauer, J.M.		Authors: Muckelbauer, J.M.

OCA: Protected "6nzf" [edit=sysop:move=sysop]

OCA — Thu, 21 Feb 2019 05:16:12 GMT

Protected "6nzf" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:16, 21 February 2019

OCA: New page: '''Unreleased structure''' The entry 6nzf is ON HOLD Authors: Muckelbauer, J.M. Description: CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH Compound_5...

OCA — Thu, 21 Feb 2019 05:16:11 GMT

New page: '''Unreleased structure''' The entry 6nzf is ON HOLD Authors: Muckelbauer, J.M. Description: CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH Compound_5...

New page

'''Unreleased structure'''

The entry 6nzf is ON HOLD

Authors: Muckelbauer, J.M.

Description: CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH Compound_5 AKA 4-[(2-CARBAMOYLPHEN YL)AMINO]-6-[(5-FLUOROPYRIDIN-2-YL)AMINO]-N-METHYLPYRIDINE -3-CARBOXAMIDE
[[Category: Unreleased Structures]]
[[Category: Muckelbauer, J.M]]