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 uracil-containing DNA by expressing an inhibitor protein (UGI) which inactivates the host uracil-DNA glycosylase (UDGase) base-excision repair enzyme. Also, PBS1/2 UGI efficiently inactivates UDGases from other biological sources, including the enzyme from herpes simplex virus type-1 (HSV-1). The crystal structure of the HSV-1 UDGase–PBS1 UGI complex at 2.7 Å reveals an α-β-α sandwich structure for UGI which interacts with conserved regions of UDGase involved in DNA binding, and directly mimics protein–DNA interactions observed in the UDGase–oligonucleotide complex. The inhibitor completely blocks access to the active site of UDGase, but makes no direct contact with the uracil-binding pocket itself.

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