CRYSTAL-STRUCTURE OF A CONSERVED PROTEASE THAT BINDS DNA - THE BLEOMYCIN HYDROLASE, GAL6

Bleomycin hydrolase is a cysteine protease that hydrolyzes the antican cer drug bleomycin. The homolog in yeast, Gal6, has recently been iden tified and found to bind DNA and to act as a repressor in the Gal4 reg ulatory system, The crystal structure of Gal6 at 2.2 Angstrom resoluti on reveals a hexameric structure with a prominent central channel, The papain-like active sites are situated within the central channel, in a manner resembling the organization of active sites in the proteasome . The Gal6 channel is lined with 60 lysine residues from the six subun its, suggesting a role in DNA binding, The carboxyl-terminal arm of Ga l6 extends into the active site cleft and may serve a regulatory funct ion. Rather than each residing in distinct, separable domains, the pro tease and DNA-binding activities appear structurally intertwined in th e hexamer, implying a coupling of these two activities.