Article
Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors.
Proceedings of the National Academy of Sciences of the United States of America - 11 Jul 2023
Akkapeddi Padma, Hattori Takamitsu, Khan Imran, Glasser Eliezra, Koide Akiko, Ketavarapu Gayatri, Whaby Michael, Zuberi Mariyam, Teng Kai Wen, Lefler Julia, Maso Lorenzo, Bang Injin, Ostrowski Michael C, O'Bryan John P, Koide Shohei
Abstract excerpt
The G12D mutation is among the most common KRAS mutations associated with cancer, in particular, pancreatic cancer. Here, we have developed monobodies, small synthetic binding proteins, that are selective to KRAS(G12D) over KRAS(wild type) and other oncogenic KRAS mutations, as well as over the G12D mutation in HRAS and NRAS. Crystallographic studies revealed that, similar to other KRAS mutant-selective...
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