Crystal structure of human cathepsin V

Cathepsin V is a lysosomal cysteine protease that is expressed in the thymu s, testis and corneal epithelium. We have determined the 1.6 Angstrom resol ution crystal structure of human cathepsin V associated with an irreversibl e vinyl sulfone inhibitor. The fold of this enzyme is similar to the fold a dopted by other members of the papain superfamily of cysteine proteases. Th is study provides a framework for understanding the structural basis for ca thepsin V's activity and will aid in the design of inhibitors of this enzym e. A comparison of cathepsin V's active site with the active sites of relat ed proteases revealed a number of differences, especially in the S2 and S3 subsites, that could be exploited in identifying specific cathepsin V inhib itors or in identifying inhibitors of other cysteine proteases that would b e selective against cathepsin V.