Contributions to the S'-subsite specificity of papain.
The product ratio was analyzed for the papain-catalyzed acyl transfer from the specific acyl donor Mal-Phe-Ala-OEtCl to various nucleophilic amino components, ranging from amino acid amides to tripeptide amides. The data obtained are discussed in terms of binding specificity. From the structure-activity relationships for the S'1-P'1 interaction it follows that only three methyl(ene) groups can be accommodated in the S'1 subsite. Hydrophilic side chains are bound better to S'1 than indicated by their hydrophobicities. Negatively charged amino components are inefficient deacylating agents. However, there was no evidence for electrostatic contributions to the nucleophile binding. Amino components with bulky hydrophobic amino acid residues in the P'2 and in the P'3 position, respectively, are preferentially bound to Mal-Phe-Ala-papain. The results of this study can be applied to the planning of papain-catalyzed peptide synthesis reactions.
Schuster
M
M
Department of Biochemistry, Leipzig University, Germany.
Kasche
V
V
Jakubke
H D
HD
D000217:Acyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D007700:Kinetics; D008433:Mathematics; D008969:Molecular Sequence Data; D009842:Oligopeptides; D010206:Papain / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011487:Protein Conformation; D013379:Substrate Specificity
D009842:Oligopeptides; D011189:Potassium Chloride; D000217:Acyltransferases; D010206:Papain