5HEZ
JAK2 kinase (JH1 domain) mutant P1057A in complex with TG101209
Summary for 5HEZ
| Entry DOI | 10.2210/pdb5hez/pdb |
| Related | 4JI9 |
| Descriptor | Tyrosine-protein kinase JAK2, CHLORIDE ION, ZINC ION, ... (5 entities in total) |
| Functional Keywords | protein kinase, inhibitor, mutation, tyk2, surrogate, p1104a, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Endomembrane system ; Peripheral membrane protein : O60674 |
| Total number of polymer chains | 4 |
| Total formula weight | 146155.39 |
| Authors | Ultsch, M.,Eigenbrot, C. (deposition date: 2016-01-06, release date: 2016-11-09, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 27807284DOI: 10.1126/scitranslmed.aag1974 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.66 Å) |
Structure validation
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