Structure and function of proparts in zymogens for aspartic proteinases

Alignment of amino-acid sequences of zymogens for aspartic proteinases shows homology among the proparts corresponding to that observed for the active enzymes. The alignment indicates that all zymogens have a lysine residue at position p36 (porcine pepsinogen numbering). In the tertiary structure of porcine pepsinogen this residue is located between the two aspartic residues that participate in the catalytic mechanism of the active enzyme. It is suggested that Lys (p36) is essential for the correct folding of the zymogen molecule. Activation models and pathways are discussed.