ABSTRACT
The process of connecting a protein’s original amino-and carboxy-
termini with a peptide linker, along with the placement of new
termini elsewhere in the protein structure by disrupting an existing
peptide bond in its backbone, results in circular permutation (CP).
Except for the introduction of additional amino acid residues
constituting the peptide linker that is joining the old ends, the amino
acid composition of the original protein is unaltered. Thus, circularly
permuted protein variants (permutants) are predominantly char-
acterized by a rearrangement of the protein sequence (Fig. 19.1).
Although in permutants the overall three-dimensional structures
of active variants compared to the native state of the original
protein are largely unchanged, modified protein dynamics can be
observed, depending on the position of the introduced backbone
fissure. In particular, relocation of the new termini in proximity to
the active center or substrate-binding sites of an enzyme affects the
conformational flexibility of the polypeptide chain and accordingly
governs catalytic performance or protein stability. According to
these characteristics, not only nature but also protein engineers took
up this intriguing conception to evolve protein function.
