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 angstrum reveals an alpha-beta-alpha 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.
Savva
R
R
Department of Biochemistry and Molecular Biology, University College, London, UK.
Pearl
L H
LH
D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001435:Bacteriophages / Q000737:chemistry; D018360:Crystallography, X-Ray; D045647:DNA Glycosylases; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D018139:Simplexvirus / Q000201:enzymology; D051981:Uracil-DNA Glycosidase; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D001426:Bacterial Proteins; D009711:Nucleotides; D014764:Viral Proteins; C027619:uracil-DNA glycosylase inhibitor protein, B. subtilis bacteriophage; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase