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<StructureSection load='6ova' size='340' side='right'caption='[[6ova]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='6ova' size='340' side='right'caption='[[6ova]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ova]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OVA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OVA FirstGlance]. <br>
<table><tr><td colspan='2'>[[6ova]] 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=6OVA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OVA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N9G:6-({4-[(3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl]pyridin-2-yl}amino)-N,N-dimethylpyridine-3-carboxamide'>N9G</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]] 2.5&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N9G:6-({4-[(3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl]pyridin-2-yl}amino)-N,N-dimethylpyridine-3-carboxamide'>N9G</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=6ova FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ova OCA], [http://pdbe.org/6ova PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ova RCSB], [http://www.ebi.ac.uk/pdbsum/6ova PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ova 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=6ova FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ova OCA], [https://pdbe.org/6ova PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ova RCSB], [https://www.ebi.ac.uk/pdbsum/6ova PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ova 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;">
== Publication Abstract from PubMed ==
Herein we report an efficient method for the synthesis of a highly functionalized 2-pyrrolidinone, tert-butyl 3-cyano-3-cyclopropyl-2-oxopyrrolidine-4-carboxylate, from readily available starting materials. Utility of this compound was demonstrated in the synthesis of a novel series of macrocyclic Tyk2 inhibitors, leading to the identification of a potent and selective macrocyclic Tyk2 inhibitor (26).


Efficient synthesis of tert-butyl 3-cyano-3-cyclopropyl-2-oxopyrrolidine-4-carboxylates: Highly functionalized 2-pyrrolidinone enabling access to novel macrocyclic Tyk2 inhibitors.,Sasaki Y, Tokuhara H, Ohba Y, Okabe A, Nakayama M, Nakagawa H, Skene R, Hoffman I, Zou H, Yoshida M Bioorg Med Chem Lett. 2020 Mar 1;30(5):126963. doi: 10.1016/j.bmcl.2020.126963., Epub 2020 Jan 13. PMID:31980341<ref>PMID:31980341</ref>
==See Also==
 
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ova" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Hoffman ID]]
[[Category: Hoffman, I D]]
[[Category: Skene RJ]]
[[Category: Skene, R J]]
[[Category: Complex]]
[[Category: Inhibitor]]
[[Category: Transferase-transferase inhibitor complex]]
Retrieved from "https://proteopedia.org/6ova"