5Y80

Complex structure of cyclin G-associated kinase with gefitinib

5Y80 の概要

• エントリーDOI: 10.2210/pdb5y80/pdb
• 分子名称: Cyclin-G-associated kinase, NANOBODY, Gefitinib, ... (4 entities in total)
• 機能のキーワード: kinase, complex, transferase-immune system complex, transferase/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52741.30

構造登録者

Ohbayashi, N.,Murayama, K.,Kato-Murayama, M.,Shirouzu, M. (登録日: 2017-08-18, 公開日: 2018-08-29, 最終更新日: 2024-10-23)

主引用文献

Ohbayashi, N.,Murayama, K.,Kato-Murayama, M.,Kukimoto-Niino, M.,Uejima, T.,Matsuda, T.,Ohsawa, N.,Yokoyoma, S.,Nojima, H.,Shirouzu, M.
Structural Basis for the Inhibition of Cyclin G-Associated Kinase by Gefitinib.
ChemistryOpen, 7:721-727, 2018

PubMed Abstract: Gefitinib is the molecular target drug for advanced non-small-cell lung cancer. The primary target of gefitinib is the positive mutation of epidermal growth factor receptor, but it also inhibits cyclin G-associated kinase (GAK). To reveal the molecular bases of GAK and gefitinib binding, structure analyses were conducted and determined two forms of the gefitinib-bound nanobody⋅GAK kinase domain complex structures. The first form, GAK_1, has one gefitinib at the ATP binding pocket, whereas the second form, GAK_2, binds one each in the ATP binding site and a novel binding site adjacent to the activation segment C-terminal helix, a unique element of the Numb-associated kinase family. In the novel binding site, gefitinib binds in the hydrophobic groove around the activation segment, disrupting the conserved hydrogen bonds for the catalytic activity. These structures suggest possibilities for the development of selective GAK inhibitors for viral infections, such as the hepatitis C virus.

PubMed: 30214852
DOI: 10.1002/open.201800177

実験手法

X-RAY DIFFRACTION (2.5 Å)