4OLI

The pseudokinase/kinase protein from JAK-family member TYK2

4OLI の概要

• エントリーDOI: 10.2210/pdb4oli/pdb
• 分子名称: Non-receptor tyrosine-protein kinase TYK2, 2-chloro-N-{2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}benzamide (3 entities in total)
• 機能のキーワード: protein kinase, phospho-transfer, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 73935.73

構造登録者

Eigenbrot, C.,Ultsch, M.,Wallweber, H. (登録日: 2014-01-23, 公開日: 2014-05-28, 最終更新日: 2023-09-20)

主引用文献

Lupardus, P.J.,Ultsch, M.,Wallweber, H.,Bir Kohli, P.,Johnson, A.R.,Eigenbrot, C.
Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition.
Proc.Natl.Acad.Sci.USA, 111:8025-8030, 2014

PubMed Abstract: Janus kinases (JAKs) are receptor-associated multidomain tyrosine kinases that act downstream of many cytokines and interferons. JAK kinase activity is regulated by the adjacent pseudokinase domain via an unknown mechanism. Here, we report the 2.8-Å structure of the two-domain pseudokinase-kinase module from the JAK family member TYK2 in its autoinhibited form. We find that the pseudokinase and kinase interact near the kinase active site and that most reported mutations in cancer-associated JAK alleles cluster in or near this interface. Mutation of residues near the TYK2 interface that are analogous to those in cancer-associated JAK alleles, including the V617F and "exon 12" JAK2 mutations, results in increased kinase activity in vitro. These data indicate that JAK pseudokinases are autoinhibitory domains that hold the kinase domain inactive until receptor dimerization stimulates transition to an active state.

PubMed: 24843152
DOI: 10.1073/pnas.1401180111

実験手法

X-RAY DIFFRACTION (2.8 Å)