5E8V

TGF-BETA RECEPTOR TYPE 2 KINASE DOMAIN (E431A,R433A,E485A,K488A,R493A,R495A)

5E8V の概要

• エントリーDOI: 10.2210/pdb5e8v/pdb
• 関連するPDBエントリー: 5E8S 5E8T 5E8U 5E8W 5E8X 5E8Y 5E8Z 5E90 5E91 5E92
• 分子名称: TGF-beta receptor type-2, GLYCEROL (3 entities in total)
• 機能のキーワード: kinase domain, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein : P37173
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35932.77

構造登録者

Sheriff, S. (登録日: 2015-10-14, 公開日: 2016-05-11, 最終更新日: 2023-09-27)

主引用文献

Tebben, A.J.,Ruzanov, M.,Gao, M.,Xie, D.,Kiefer, S.E.,Yan, C.,Newitt, J.A.,Zhang, L.,Kim, K.,Lu, H.,Kopcho, L.M.,Sheriff, S.
Crystal structures of apo and inhibitor-bound TGF beta R2 kinase domain: insights into TGF beta R isoform selectivity.
Acta Crystallogr D Struct Biol, 72:658-674, 2016

PubMed Abstract: The cytokine TGF-β modulates a number of cellular activities and plays a critical role in development, hemostasis and physiology, as well as in diseases including cancer and fibrosis. TGF-β signals through two transmembrane serine/threonine kinase receptors: TGFβR1 and TGFβR2. Multiple structures of the TGFβR1 kinase domain are known, but the structure of TGFβR2 remains unreported. Wild-type TGFβR2 kinase domain was refractory to crystallization, leading to the design of two mutated constructs: firstly, a TGFβR1 chimeric protein with seven ATP-site residues mutated to their counterparts in TGFβR2, and secondly, a reduction of surface entropy through mutation of six charged residues on the surface of the TGFβR2 kinase domain to alanines. These yielded apo and inhibitor-bound crystals that diffracted to high resolution (<2 Å). Comparison of these structures with those of TGFβR1 reveal shared ligand contacts as well as differences in the ATP-binding sites, suggesting strategies for the design of pan and selective TGFβR inhibitors.

PubMed: 27139629
DOI: 10.1107/S2059798316003624

実験手法

X-RAY DIFFRACTION (1.69 Å)