Macromolecular Therapeutics

Computer-assisted design of a novel transcription factor for the BAX gene.

The BAX promoter contains sites for the binding of both p53 and of zinc finger transcription factors. The structure of the DNA-binding domain of p53 (blue) and of a zinc finger from the SP1 transcription factor (purple) were obtained from protein structure data banks. The protein domains were docked onto double-stranded DNA (yellow) using a molecular modeling program. A polypeptide linker (green) was designed to optimally position both DNA-binding domains onto the promoter. A transactivating domain was also added (not shown). The information from modeling was incorporated into the design of a vector to express the chimeric protein (see text for details; unpublished work).