The human cellular protein APOBEC3F (A3F) is capable of mutating the DNA of the AIDS virus HIV rendering it nonfunctional and incapable of replication. A3F enters virus particles during reverse transcription and converts viral cDNA cytosines to uracils, which template the insertion of adenines instead of guanines and result in strand-specific mutations. However, A3F does not normally have a chance to be effective because it is antagonized by a small HIV-1 protein called Vif, which triggers the degradation of A3F. Nevertheless, the A3F mutagenic signature is still found within the DNA of the HIV-1 virus itself, indicating that the antiviral activity of this protein can manifest in vivo (in people) and that therapeutics that stimulate this activity may be beneficial. We hypothesize that a high-resolution structure of A3F will provide crucial information that will enable the rational design of compounds that disrupt the A3F-Vif interaction. To achieve this goal, we first identified the minimal region of A3F that is both catalytic and and able to bind Vif. Second, we improved the activity of this construct using structure-guided mutagenesis. Third, we are presently optimizing purification conditions to improve solubility.