7C41

KRAS G12V and H-REV107 peptide complex

7C41 の概要

• エントリーDOI: 10.2210/pdb7c41/pdb
• 分子名称: GTPase KRas, HRAS-like suppressor 3, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: kras g12v, h-rev107, inhibitor, structural protein, oncoprotein-hydrolase complex, oncoprotein/hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 83055.39

構造登録者

Han, C.W.,Jeong, M.S.,Jang, S.B. (登録日: 2020-05-14, 公開日: 2021-05-19, 最終更新日: 2023-11-29)

主引用文献

Han, C.W.,Jeong, M.S.,Ha, S.C.,Jang, S.B.
A H-REV107 Peptide Inhibits Tumor Growth and Interacts Directly with Oncogenic KRAS Mutants.
Cancers (Basel), 12:-, 2020

PubMed Abstract: Kirsten-RAS (KRAS) has been the target of drugs because it is the most mutated gene in human cancers. Because of the low affinity of drugs for KRAS mutations, it was difficult to target these tumor genes directly. We found a direct interaction between KRAS G12V and tumor suppressor novel H-REV107 peptide with high binding affinity. We report the first crystal structure of an oncogenic mutant, KRAS G12V-H-REV107. This peptide was shown to interact with KRAS G12V in the guanosine diphosphate (GDP)-bound inactive state and to form a stable complex, blocking the activation function of KRAS. We showed that the peptide acted as an inhibitor of mutant KRAS targets by [α-P] guanosine triphosphate (GTP) binding assay. The H-REV107 peptide inhibited pancreatic cancer and colon cancer cell lines in cell proliferation assay. Specially, the H-REV107 peptide can suppress pancreatic tumor growth by reduction of tumor volume and weight in xenotransplantation mouse models. Overall, the results presented herein will facilitate development of novel drugs for inhibition of KRAS mutations in cancer patients.

PubMed: 32486141
DOI: 10.3390/cancers12061412

実験手法

X-RAY DIFFRACTION (2.276 Å)