Figure 1.

Design of tetranuclear clusters in helix bundles. a) D₂-symmetrical 4DH analogues, bearing the DXXH metal-binding motif, have four Asp and four His residues coordinating 4 ions at the core. Second-shell Asp residues at the c–g interface (shown in red) are included to interact with the first-shell His ligands. The positions of the three orthogonal two-fold axes are also indicated. b) Crystal structure of 4DH1 (PDB ID 5WLL): the main chain is presented as cartoon, zinc ions as spheres, and coordinating residues as sticks. c) Designed tetranuclear zinc cluster, showing the relative orientations among the carboxylates. d) Model structure of 4DH analogues, including the first-shell ligands Asp¹² and His¹⁶, the second-shell Asp¹¹, and the third-shell Arg¹⁴. e) Sequence alignment of 4DH analogues. Coordinating residues are in bold, while b and e positions in proximity of the metal-binding site are underlined.