Entrapment and structure of an extrahelical guanine attempting to enter the active site of a bacterial DNA glycosylase, MutM.
MutM, a bacterial DNA glycosylase, protects genome integrity by catalyzing glycosidic bond cleavage of 8-oxoguanine (oxoG) lesions, thereby initiating base excision DNA repair. The process of searching for and locating oxoG lesions is especially challenging, because of the close structural resemblance of oxoG to its million-fold more abundant progenitor, G. Extrusion of the target nucleobase from the DNA double helix to an extrahelical position is an essential step in lesion recognition and catalysis by MutM. Although the interactions between the extruded oxoG and the active site of MutM have been well characterized, little is known in structural detail regarding the interrogation of extruded normal DNA bases by MutM. Here we report the capture and structural elucidation of a complex in which MutM is attempting to present an undamaged G to its active site. The structure of this MutM-extrahelical G complex provides insights into the mechanism MutM employs to discriminate against extrahelical normal DNA bases and into the base extrusion process in general.
Qi
Yan
Y
Graduate Program in Biophysics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Spong
Marie C
MC
Nam
Kwangho
K
Karplus
Martin
M
Verdine
Gregory L
GL
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D020134:Catalytic Domain / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D043382:DNA-Formamidopyrimidine Glycosylase / Q000737:chemistry* / Q000378:metabolism; D016680:Genome, Bacterial / Q000502:physiology; D001411:Geobacillus stearothermophilus / Q000201:enzymology*; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology
D001426:Bacterial Proteins; D004269:DNA, Bacterial; C024829:8-hydroxyguanine; D006147:Guanine; D043382:DNA-Formamidopyrimidine Glycosylase