Binding specificity of papain and cathepsin B.
In order to obtain useful information for the design of inhibitors of cathepsin B, an important enzyme in both physiological and pathological processes, the modes of interaction between ligands and thiol proteases (papain and cathepsin B) were analyzed. A new and powerful method was developed to quantitatively understand geometrical features of the interaction. Fairly good electrostatic complementarities were found for the oxygen atoms of P1 and P2 amide, and for the hydrogen atom of P2 amide. Electrostatic correlation potentials on the side chains of P1 and P2 were nearly neutral, so that interacting conformations in these regions are anticipated to be stabilized by hydrophobic forces rather than electrostatic ones. A three-dimensional structure of rat liver cathepsin B was deduced based on the assumption that the tertiary structure of cathepsin B is similar to that of actinidin. Furthermore, an inhibitor of the thiol proteases, benzyloxycarbonyl-L-phenylalanyl-L-alanine chloromethyl ketone was model fitted to cathepsin B, in order to investigate its mode of interaction with the enzyme. It was possible to account for some structure-activity relationships in the enzyme-ligand interactions.
D000595:Amino Acid Sequence; D001665:Binding Sites; D002401:Cathepsin B / Q000378:metabolism*; D003196:Computer Graphics; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism; D008958:Models, Molecular; D010206:Papain / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013379:Substrate Specificity
D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C018745:actinidain; D010206:Papain