Effect of polymer size on the inhibition of protocollagen proline hydroxylase by polyproline II.

Fractions of poly-L-proline Form II ranging in molecular weight from 1,600 to 21,000 were compared in their ability to serve as competitive inhibitors for the synthesis of hydroxyproline by protocollagen proline hydroxylase. The degree of inhibition of the enzyme increased with the size of the polymer, and the Ki values decreased progressively with molecular weight. The results indicated that poly-Lproline polymers with 150 to 200 residues have higher aflinities for the inhibitor site or sites on the enzyme than smaller poly-L-proline fractions with the same structure in solution. The data could not be explained solely on the basis that large fractions of poly-L-proline act as multifunctional reactants with cooperative or noncooperative binding of several enzyme molecules per polypeptide. Accordingly, it appears that interaction between the enzyme and poly-L-proline involves some unusual feature such as an inhibitor site large enough to accommodate 150 to 200 prolyl residues or lateral movement of the enzyme along the polypeptide.