3nyx: Difference between revisions
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< | ==Non-phosphorylated TYK2 JH1 domain with Quinoline-Thiadiazole-Thiophene Inhibitor== | ||
<StructureSection load='3nyx' size='340' side='right'caption='[[3nyx]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3nyx]] 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=3NYX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NYX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=TZ1:N-{5-[(7-CHLOROQUINOLIN-4-YL)SULFANYL]-1,3,4-THIADIAZOL-2-YL}THIOPHENE-2-CARBOXAMIDE'>TZ1</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=3nyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nyx OCA], [https://pdbe.org/3nyx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nyx RCSB], [https://www.ebi.ac.uk/pdbsum/3nyx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nyx ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[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 == | |||
[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;"> | |||
== Publication Abstract from PubMed == | |||
Members of the JAK family of protein kinases mediate signal transduction from cytokine receptors to transcription factor activation. Over-stimulation of these pathways is causative in immune disorders like rheumatoid arthritis, psoriasis, lupus, and Crohn's disease. A search for selective inhibitors of a JAK kinase has led to our characterization of a previously unknown kinase conformation arising from presentation of Tyr962 of TYK2 to an inhibitory small molecule via an H-bonding interaction. A small minority of protein kinase domains has a Tyrosine residue in this position within the alphaC-beta4 loop, and it is the only amino acid commonly seen here with H-bonding potential. These discoveries will aid design of inhibitors that discriminate among the JAK family and more widely among protein kinases. Proteins 2010. (c) 2010 Wiley-Liss, Inc. | |||
A new regulatory switch in a JAK protein kinase.,Tsui V, Gibbons P, Ultsch M, Mortara K, Chang C, Blair W, Pulk R, Stanley M, Starovasnik M, Williams D, Lamers M, Leonard P, Magnuson S, Liang J, Eigenbrot C Proteins. 2010 Oct 7. PMID:21117080<ref>PMID:21117080</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3nyx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[ | |||
== | |||
< | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Eigenbrot | [[Category: Eigenbrot C]] | ||
[[Category: Ultsch | [[Category: Ultsch M]] | ||
Latest revision as of 12:24, 6 September 2023
Non-phosphorylated TYK2 JH1 domain with Quinoline-Thiadiazole-Thiophene InhibitorNon-phosphorylated TYK2 JH1 domain with Quinoline-Thiadiazole-Thiophene Inhibitor
Structural highlights
DiseaseTYK2_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: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. FunctionTYK2_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.[1] Publication Abstract from PubMedMembers of the JAK family of protein kinases mediate signal transduction from cytokine receptors to transcription factor activation. Over-stimulation of these pathways is causative in immune disorders like rheumatoid arthritis, psoriasis, lupus, and Crohn's disease. A search for selective inhibitors of a JAK kinase has led to our characterization of a previously unknown kinase conformation arising from presentation of Tyr962 of TYK2 to an inhibitory small molecule via an H-bonding interaction. A small minority of protein kinase domains has a Tyrosine residue in this position within the alphaC-beta4 loop, and it is the only amino acid commonly seen here with H-bonding potential. These discoveries will aid design of inhibitors that discriminate among the JAK family and more widely among protein kinases. Proteins 2010. (c) 2010 Wiley-Liss, Inc. A new regulatory switch in a JAK protein kinase.,Tsui V, Gibbons P, Ultsch M, Mortara K, Chang C, Blair W, Pulk R, Stanley M, Starovasnik M, Williams D, Lamers M, Leonard P, Magnuson S, Liang J, Eigenbrot C Proteins. 2010 Oct 7. PMID:21117080[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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