PDBsum entry 5hez

Transferase/transferase inhibitor

PDB id: 5hez

Contents

Protein chains

289 a.a.

Ligands

1M3 ×8

Metals

_ZN ×2

_CL ×3

Waters ×110

PDB id:

5hez

Name:

Transferase/transferase inhibitor

Title:

Jak2 kinase (jh1 domain) mutant p1057a in complex with tg101209

Structure:

Tyrosine-protein kinase jak2. Chain: a, b, c, d. Synonym: janus kinase 2,jak-2. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: jak2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.66Å R-factor: 0.218 R-free: 0.238

Authors:

M.Ultsch,C.Eigenbrot

Key ref:

C.A.Dendrou et al. (2016). Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med, 8, 363ra149. PubMed id: 27807284

Date:

06-Jan-16 Release date: 09-Nov-16

Protein chains

O60674  (JAK2_HUMAN) -  Tyrosine-protein kinase JAK2 from Homo sapiens

Seq: 1132 a.a.

Struc: 289 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Sci Transl Med 8:363ra149 (2016)

PubMed id: 27807284

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.

C.A.Dendrou, A.Cortes, L.Shipman, H.G.Evans, K.E.Attfield, L.Jostins, T.Barber, G.Kaur, S.B.Kuttikkatte, O.A.Leach, C.Desel, S.L.Faergeman, J.Cheeseman, M.J.Neville, S.Sawcer, A.Compston, A.R.Johnson, C.Everett, J.I.Bell, F.Karpe, M.Ultsch, C.Eigenbrot, G.McVean, L.Fugger.

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.