5E90

TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D,I211V,Y249F, S280T,Y282F,S287N,A350C,L352F) IN COMPLEX WITH 3-AMINO-6- [4-(2-HYDROXYETHYL)PHENYL]-N-[4-(MORPHOLIN-4-YL)PYRIDIN-3-YL]PYRAZINE-2-CARBOXAMIDE

5E90 の概要

• エントリーDOI: 10.2210/pdb5e90/pdb
• 関連するPDBエントリー: 5E8S 5E8T 5E8U 5E8V 5E8W 5E8X 5E8Y 5E8Z 5E91 5E92
• 分子名称: TGF-beta receptor type-1, 3-amino-6-[4-(2-hydroxyethyl)phenyl]-N-[4-(morpholin-4-yl)pyridin-3-yl]pyrazine-2-carboxamide (3 entities in total)
• 機能のキーワード: alk5, sb431542, kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein : P36897
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35647.04

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 (2.05 Å)