Alignment of IκBα Ank3 and p53BP2/ASPP2 Ank5 structures are consistent with a shared binding mechanism between NF-κB binding ankyrins and p53 binding ankyrins that could be targeted by ZANK. IκBα Ank3 (green) is shown superimposed on p53bp2/ASPP2 Ank5 (Salmon). P53bp2/ASPP2 Ank5 is similar in length to NF-κB binding short ankyrin loops but also shares structural features spatially conserved in location and orientation to long ankyrin loops such as IκBα Ank3. p53BP2/ASPP2 Ank5 aa Tyr 424 aligns structurally a with IκBα Ank3Tyr 181 (filled blue arrow). The terminal residue of ZANK (Tyr 245) could substitute for highly conserved aromatic tyrosine binding interaction between IκBα Ank3 tyr 181 and NF-κB, as well as coordinating corresponding interactions between ZANK and p53. Both short and long ankyrins and P53bp2/ASPP2 Ank5 share a highly conserved histidine corresponding to IκBα Ank3 aa His 149 (dark blue arrow). A corresponding residue is present in ZANK (Val 203). P53bp2/ASPP2 Ank5 lacks a residue corresponding to IκBα Ank3 aa His 184 (narrow stem blue arrow), but a corresponding residue (His 239) is present in ZANK.