Leemor Joshua-Tor, Ph.D., Cold Spring Harbor Laboratory Crystal structure of Gal6, the yeast bleomycin hydrolase. The protein consists of six identical subunits, each of which is shown in a different color. We study the molecular basis of cell regulatory processes by using the tools of structural biology and biochemistry to examine proteins and protein complexes associated with these processes. Our current efforts center around two distinct themes. The first is the regulation of proteolysis.
Caspases are cysteine proteases that play a central role in apoptosis.
They are expressed as inactive zymogens or precursors which, when activated, are part of an irreversible proteolytic cascade. We also study a conserved family of self-compartmentalizing cysteine proteases, the bleomycin hydrolases. These proteases are able to hydrolyze the anticancer drug bleomycin, thus limiting its use in the treatment of human cancer. They use the positioning of their carboxy terminus to control substrate recognition and proteolytic activity. The second theme in the lab involves structural studies of protein complexes involved in DNA regulatory processes.