5HEZ

JAK2 kinase (JH1 domain) mutant P1057A in complex with TG101209

5HEZ の概要

• エントリーDOI: 10.2210/pdb5hez/pdb
• 関連するPDBエントリー: 4JI9
• 分子名称: Tyrosine-protein kinase JAK2, CHLORIDE ION, ZINC ION, ... (5 entities in total)
• 機能のキーワード: protein kinase, inhibitor, mutation, tyk2, surrogate, p1104a, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Endomembrane system ; Peripheral membrane protein : O60674
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 146155.39

構造登録者

Ultsch, M.,Eigenbrot, C. (登録日: 2016-01-06, 公開日: 2016-11-09, 最終更新日: 2024-11-06)

主引用文献

Dendrou, C.A.,Cortes, A.,Shipman, L.,Evans, H.G.,Attfield, K.E.,Jostins, L.,Barber, T.,Kaur, G.,Kuttikkatte, S.B.,Leach, O.A.,Desel, C.,Faergeman, S.L.,Cheeseman, J.,Neville, M.J.,Sawcer, S.,Compston, A.,Johnson, A.R.,Everett, C.,Bell, J.I.,Karpe, F.,Ultsch, M.,Eigenbrot, C.,McVean, G.,Fugger, L.
Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.
Sci Transl Med, 8:363ra149-363ra149, 2016

PubMed Abstract: Thousands of genetic variants have been identified, which contribute to the development of complex diseases, but determining how to elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders; subsequent molecular, cellular, in vivo, and structural functional follow-up; and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for certain common autoimmune disorders.

PubMed: 27807284
DOI: 10.1126/scitranslmed.aag1974

実験手法

X-RAY DIFFRACTION (2.66 Å)