6ZL3

CRYSTAL STRUCTURE OF HRAS IN COMPLEX WITH COMPOUND 18 and GDP

6ZL3 の概要

• エントリーDOI: 10.2210/pdb6zl3/pdb
• 分子名称: GTPase HRas, SODIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: gtpase, hydrolase
• 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: 19719.81

構造登録者

Kessler, D.,Fischer, G.,Boettcher, J. (登録日: 2020-06-30, 公開日: 2020-08-19, 最終更新日: 2024-01-31)

主引用文献

Kessler, D.,Bergner, A.,Bottcher, J.,Fischer, G.,Dobel, S.,Hinkel, M.,Mullauer, B.,Weiss-Puxbaum, A.,McConnell, D.B.
Drugging all RAS isoforms with one pocket.
Future Med Chem, 12:1911-1923, 2020

PubMed Abstract: Activating mutations in the three human RAS genes, , and , are among the most common oncogenic drivers in human cancers. Covalent KRAS inhibitors, which bind to the switch II pocket in the 'off state' of KRAS, represent the first direct KRAS drugs that entered human clinical trials. However, the remaining 85% of non-KRAS-driven cancers remain undrugged as do NRAS and HRAS and no drugs targeting the 'on state' have been discovered so far. The switch I/II pocket is a second pocket for which the nanomolar inhibitor BI-2852 has been discovered. Here, we elucidate inhibitor binding modes in KRAS, NRAS and HRAS on and off and discuss future strategies to drug all RAS isoforms with this one pocket.

PubMed: 32779487
DOI: 10.4155/fmc-2020-0221

実験手法

X-RAY DIFFRACTION (2.031 Å)