NUCLEOTIDE MIMICRY IN THE CRYSTAL-STRUCTURE OF THE URACIL-DNA GLYCOSYLASE-URACIL GLYCOSYLASE INHIBITOR PROTEIN COMPLEX

The Bacillus subtilis bacteriophages PBS-1 and PBS-2 protect their ura cil-containing DNA by expressing an inhibitor protein (UGI) which inac tivates the host uracil-DNA glycosylase (UDGase) base-excision repair enzyme. Also, PBS?IZ UGI efficiently inactivates UDGases from other bi ological sources, including the enzyme from herpes simplex virus type- 1 (HSV-1). The crystal structure of the HSV-1 UDGase-PBS1 UGl complex at 2.7 Angstrom reveals an alpha-beta-alpha sandwich structure for UGI which interacts with conserved regions of UDGase involved in DNA bind ing, and directly mimics protein-DNA interactions observed in the UDGa se-oligonucleotide complex. The inhibitor completely blocks access to the active site of UDGase, but makes no direct contact with the uracil -binding pocket itself.