Cyclotides are fascinating circular proteins ranging from 28 to 37 aa residues that are naturally expressed in plants. They exhibit antimicrobial, insecticidal, antihelmintic, cytotoxic, and antiviral activities (1), and protease inhibitory activity (2), and can exert uterotonic effects (3). They all share a unique head-to-tail circular knotted topology of three disulfide bridges, with one disulfide bond penetrating through a macrocycle formed by the other two disulfides bonds and interconnecting peptide backbones, forming what is called a cystine knot topology (Fig. 1) (1). This cyclic cystine knot framework gives cyclotides a compact, highly rigid structure (4), which confers exceptional resistance to...
Natural Sciences in General