Tertiary structures of a neutrophil-derived antimicrobial protein and peptide in clinical trials.

(A) BPI has a bipartite structure characterized by 2-fold symmetry that gives the molecule a “boomerang” shape. Cationic amino acid residues (purple) are concentrated in the N-terminal half of the molecule, which carries the endotoxin-neutralizing and bactericidal activities of the protein. A recombinant N-terminal BPI fragment is currently in clinical trials. The C-terminal half of BPI is required for opsonic activity. Two apolar sites thought to be important for interaction with lipids are indicated in green. (B) The protegrin peptide, which is derived from a cathelicidin precursor, is composed of 18 amino acids. Four cysteine residues form 2 disulfide bonds (yellow), giving the peptide a hairpin structure. Six cationic arginine residues are indicated in red.