Inhibition of serine proteinases belonging to the chymotrypsin superfamily by the cyclic thiolic compound YS3025: a comparative crystallographic study.

The synthetic cyclic thiolic compound 3-[2-(2-thiophencarboxythio)]-propanoyl-4-thiazolidin carboxylic acid (YS3025) acts as an effective inhibitor of bovine alpha-chymotrypsin. In the present communication YS3025 binding studies are extended to bovine beta-trypsin and porcine pancreatic elastase, by means of crystallographic difference Fourier techniques. For all the enzymes considered, the thiopencarbonyl moiety of YS3025 is located at the entrance of the inhibited proteinase primary specificity pocket (S1), covalently linked to the catalytic Ser195 OG atom, and forming an acyl-enzyme complex. These observations allow to select between alternative binding (and inhibition) mechanisms for YS3025 and related molecules to serine proteinases belonging to the chymotrypsin superfamily.