Ontology highlight
ABSTRACT:
SUBMITTER: Teng KW
PROVIDER: S-EPMC8113534 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Teng Kai Wen KW Tsai Steven T ST Hattori Takamitsu T Fedele Carmine C Koide Akiko A Yang Chao C Hou Xuben X Zhang Yingkai Y Neel Benjamin G BG O'Bryan John P JP Koide Shohei S
Nature communications 20210511 1
Activating mutants of RAS are commonly found in human cancers, but to date selective targeting of RAS in the clinic has been limited to KRAS(G12C) through covalent inhibitors. Here, we report a monobody, termed 12VC1, that recognizes the active state of both KRAS(G12V) and KRAS(G12C) up to 400-times more tightly than wild-type KRAS. The crystal structures reveal that 12VC1 recognizes the mutations through a shallow pocket, and 12VC1 competes against RAS-effector interaction. When expressed intra ...[more]