FIGURE 1. Homology modeling of the furin propeptide.

A, multiple sequence alignment between propeptides of the PC family. Predicted secondary structure of the furin propeptide and sequence conservation (black highlight, 100% similarity; dark gray highlight, >80% similarity, light gray highlight, >50% similarity) between PCs is depicted. Propep-tide residues are numbered in reference to the furin propeptide, which begins at Gln²⁵ (18). B, ribbon representation of the furin propeptide structure obtained by homology modeling. His⁶⁶ and His⁶⁹ (blue) and Arg⁷⁵ (red) are highlighted. C, surface representation of the propeptide-furin complex. The modeled propeptide (yellow) is docked onto the active site of furin (green). The internal propeptide cleavage site (red) and His⁶⁹ (blue) are highlighted. D, surface representation of the secondary cleavage site illustrates His⁶⁹ (blue) buried in the solvent-accessible pocket formed by Gly⁵³, Phe⁵⁴, Leu⁵⁵, Phe⁶⁷, and Trp⁶⁸ hydrophobic residues (yellow).