The present invention is based on the therapeutic potential of a reduced
form of thionein. Accordingly, the invention features modified
metallothionein or thionein proteins, for example, where at least one
sulfur atom is substituted with selenium (e.g., a cysteine substituted
with selenocysteine), and fragments thereof. The invention also features
methods for screening for candidate compounds that (i) decrease binding
of metal (e.g., zinc) to metallothionein or thionein and (ii) do not
change the oxidation state of metallothionein, thionein, or another
protein. Also featured are methods for generating modified thionein
proteins with reduced metal affinity and methods for treating patients
with a disease associated with oxidative stress.