Structural insights into lesion recognition and repair by the bacterial 8-oxoguanine DNA glycosylase MutM.
MutM is a bacterial 8-oxoguanine glycosylase responsible for initiating base-excision repair of oxidized guanine residues in DNA. Here we report five different crystal structures of MutM-DNA complexes that represent different steps of the repair reaction cascade catalyzed by the protein and also differ in the identity of the base opposite the lesion (the 'estranged' base). These structures reveal that the MutM active site performs the multiple steps of base-excision and 3' and 5' nicking with minimal rearrangement of the DNA backbone.
Fromme
J Christopher
JC
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Verdine
Gregory L
GL
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D016963:Thermus thermophilus / Q000201:enzymology*
D009097:Multienzyme Complexes; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase