Figure 7.

Structures of cyclized enzymes (blue spheres: active site residues, yellow: protein termini, orange: crosslinking sites). Arrows indicate the ligation site for macrocyclization: (a) Crystal structure of β‐lactamase (TEM‐1, PDB ID 1fqg)^[88] showing the introduced modifications resulting from macrocyclizations via EPL (top),^[30] isopeptide formation (middle, introduction of 23 and 12 amino acids respectively)^[57] and an unnatural amino acid (bottom, disulfide‐bridge between cysteine and tyrosine derivative SbuY at positions 65 and 184, respectively).^[71] (b) NMR structure of Sortase A (PDB ID 1ija)^[89] showing the introduced modifications resulting from macrocyclizations via a split intein (top),^[38] enzymatic ligation (middle, 19‐mer linker sequence: GSSHHHHHHSSGLVPRGSH),^[49] and INCYPRO (bottom, with Cys111, Cys149 and Cys177).^[50]