WD40-repeat (WDR) domain proteins play a crucial role in mediating protein–protein interactions that sustain oncogenesis in human cancers. One prominent example is the interaction between the transcription factor MYC and its chromatin co-factor, WD40-repeat domain protein 5 (WDR5), which is essential for oncogenic processes. The MYC family of proteins is frequently overexpressed in various cancers and has been validated as a promising target for anticancer therapies. The recruitment of MYC to chromatin is facilitated by WDR5, highlighting the significance of their interaction. Consequently, inhibiting the MYC–WDR5 interaction has been shown to induce the regression of malignant tumors, offering an alternative approach to targeting MYC in the development of anticancer drugs. WDR5 has two protein interaction sites, the “WDR5-binding motif” (WBM) site for MYC interaction and the histone methyltransferases SET1 recognition motif “WDR5-interacting” (WIN) site forming MLL complex. Significant efforts have been dedicated to the discovery of inhibitors that target the WDR5 protein. More recently, the successful application of targeted protein degradation technology has enabled the removal of WDR5. This breakthrough has opened up new avenues for inhibiting the interaction between WDR5 and the binding partners. In this review, we address the recent progress made in targeting WDR5 to inhibit MDR5–MYC and MDR5–MLL1 interactions, including its targeted protein degradation and their potential impact on anticancer drug discovery.

Bacteria and archaea respond and adapt to environmental stress conditions by modulating the toxin–antitoxin (TA) system for survival. Within the bacterium Helicobacter pylori, the protein HP0894 is a key player in the HP0894-HP0895 TA system, in which HP0894 serves as a toxin and HP0895 as an antitoxin. HP0894 has intrinsic ribonuclease (RNase) activity that regulates gene expression and translation, significantly influencing bacterial physiology and survival. This activity is influenced by the presence of metal ions such as Mg²⁺. In this study, we explore the metal-dependent RNase activity of HP0894. Surprisingly, all tested metal ions lead to a reduction in RNase activity, with zinc ions (Zn²⁺) causing the most significant decrease. The secondary structure of HP0894 remained largely unaffected by Zn²⁺ binding, whereas structural rigidity was notably increased, as revealed using CD analysis. NMR characterized the Zn²⁺ binding, implicating numerous His, Asp, and Glu residues in HP0894. In summary, these results suggest that metal ions play a regulatory role in the RNase activity of HP0894, contributing to maintaining the toxin molecule in an inactive state under normal conditions.