研究动态
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野生型人 K-Ras 及其与 GTP 结合的致癌突变体 G12D 和 G12C 的 NMR 1H、13C、15N 主链共振归属。

NMR 1H, 13C, 15N backbone resonance assignments of wild-type human K-Ras and its oncogenic mutants G12D and G12C bound to GTP.

发表日期:2023 Nov 10
作者: Chunhua Yuan, Alexandar L Hansen, Lei Bruschweiler-Li, Rafael Brüschweiler
来源: PHARMACOLOGY & THERAPEUTICS

摘要:

人类 K-Ras 蛋白是 GTPase Ras 家族的成员,可将 GTP 水解为 GDP,并同时从活性状态转变为非活性状态。它是一种关键的癌蛋白,因为多种突变,特别是残基位置 12 的突变,在多种人类癌症中频繁发生。因此,K-Ras 蛋白是开发治疗性抗癌药物的重要靶点。在这项工作中,我们报告了 GTP 复合活性形式中野生型和致癌 G12C 和 G12D 突变体几乎完整的序列特异性共振分配,包括功能上重要的 Switch I 和 Switch II 区域。这些作业是对野生型 K-Ras 及其 G12 突变体进行全面功能动力学研究的基础。© 2023。作者获得 Springer Nature B.V. 的独家许可。
Human K-Ras protein, which is a member of the GTPase Ras family, hydrolyzes GTP to GDP and concomitantly converts from its active to its inactive state. It is a key oncoprotein, because several mutations, particularly those at residue position 12, occur with a high frequency in a wide range of human cancers. The K-Ras protein is therefore an important target for developing therapeutic anti-cancer agents. In this work we report the almost complete sequence-specific resonance assignments of wild-type and the oncogenic G12C and G12D mutants in the GTP-complexed active forms, including the functionally important Switch I and Switch II regions. These assignments serve as the basis for a comprehensive functional dynamics study of wild-type K-Ras and its G12 mutants.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.