4gj2

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Template:STRUCTURE 4gj2

Contents

Tyk2 (JH1) in complex with 2,6-dichloro-N-[2-({[(1R,2R)-2-fluorocyclopropyl]carbonyl}amino)pyridin-4-yl]benzamide

Template:ABSTRACT PUBMED 23668484

Disease

[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: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

[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.[1]

About this Structure

4gj2 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Liang J, van Abbema A, Balazs M, Barrett K, Berezhkovsky L, Blair W, Chang C, Delarosa D, Devoss J, Driscoll J, Eigenbrot C, Ghilardi N, Gibbons P, Halladay J, Johnson A, Kohli PB, Lai Y, Liu Y, Lyssikatos J, Mantik P, Menghrajani K, Murray J, Peng I, Sambrone A, Shia S, Shin Y, Smith J, Sohn S, Tsui V, Ultsch M, Wu LC, Xiao Y, Yang W, Young J, Zhang B, Zhu BY, Magnuson S. Lead Optimization of a 4-Aminopyridine Benzamide Scaffold To Identify Potent, Selective, and Orally Bioavailable TYK2 Inhibitors. J Med Chem. 2013 Jun 13;56(11):4521-36. doi: 10.1021/jm400266t. Epub 2013 May 29. PMID:23668484 doi:10.1021/jm400266t
  1. ↑ Colamonici O, Yan H, Domanski P, Handa R, Smalley D, Mullersman J, Witte M, Krishnan K, Krolewski J. Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase. Mol Cell Biol. 1994 Dec;14(12):8133-42. PMID:7526154

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