2025年2月1日 · The backbone resonance assignment of HRAS-GDP and KRAS-GDP was performed using CBCANH and CBCACONH spectra assisted by a 3D NOESY-15 N-HSQC spectrum for a 0.8 mM uniformly 13 C, 15 N-labelled protein sample in the presence of 1.6 mM Mg 2+. The 3D NOESY-15 N-HSQC spectrum was recorded with a mixing time of 80 ms. In this way, complete ...

2024年8月28日 · To determine ligand binding, we monitored the changes in the 1 H and 15 N chemical shifts in 1 H– 15 N HSQC spectra. The addition of compounds C53 and Z86 to GDP-bound KRAS G12D led to chemical shift perturbations (CSPs) of a similar set of peaks, indicative of an identical binding site for the two compounds (Figure 4A and Supplementary ...

2025年1月22日 · 15 N-labeled KRAS-G12D (residues 1–169) protein was used to record 1 H– 15 N transverse relaxation optimized spectroscopy (TROSY) heteronuclear single quantum coherence (HSQC) spectra in the ...

Active KRAS is found to exist in equilibrium between two rapidly interconverting conformational states (State1-State2) in solution. Due to this dynamic feature of the protein, the 1 H- 15 N correlation cross-peak signals of several amino acid (AA) residues of KRAS belonging to the flexible loop regions are absent from its 2D 1 H- 15 N HSQC ...

2021年11月1日 · e Overlaid 1 H-15 N HSQC NMR spectra of wild-type KRAS (WT) and the Q61H mutant, as well as their phosphorylated forms (pWT and pQ61H). Peaks for selected Switch I and II residues are expanded on ...

2021年10月22日 · A good dispersion of 1 H– 15 N correlation cross-peaks as witnessed in the 2D 1 H– 15 N HSQC spectra of KRAS T35S/C118S− GppNHp (Fig. 1A) and of KRAS T35S/Q61L/C118S− GppNHp (Fig. 1B) indicates that these proteins adopt a well-folded conformation in solution. High resolution NMR data allowed unambiguous chemical-shift assignments for a ...

2019年8月8日 · Using HSQC NMR to explore specific KRas G12D structural changes in the presence of DCAI, we observed evidence of previously unreported chemical shifts in KRas G12D α-helices 1 and 3 (Fig. 4A). The HSQC spectra in the presence of fragment 18 clearly localized to a single distinct region in the SOS binding pocket (Fig. 4A).

2021年10月22日 · A good dispersion of 1 H– 15 N correlation cross-peaks as witnessed in the 2D 1 H– 15 N HSQC spectra of KRAS T35S/C118S− GppNHp (Fig. 1 A) and of KRAS T35S/Q61L/C118S− GppNHp (Fig. 1 B) indicates that these proteins adopt a well-folded conformation in solution. High resolution NMR data allowed unambiguous chemical-shift assignments for ...

2020年9月9日 · 1 H-15 N HSQC of 15 N-enriched RAS in the presence of the GEF catalytic domain of SOS (SOS cat) was used to monitor amide peaks associated with either the GTP- or GDP-bound state of KRAS. Zoom of HSQC highlighting change over time of S118 and S145 NH resonances resulting from exchange of GDP for GTP.

2023年12月17日 · 然后用 HSQC-NMR 方法筛选了约13,000个fragments，得到表1的hit分子 (图3)，最好的活性116 μM (HSQC Kd)。 图3 筛出的fragment hit分子. 其实筛出的这几个片段，跟礼来KRAS分子的back pocket部分有些像，但BI当时做的时候，礼来分子应该尚未公开。