title: Structures of endonuclease V with DNA reveal initiation of deaminated adenine repair.
abstract: Endonuclease V (EndoV) initiates a major base-repair pathway for nitrosative deamination resulting from endogenous processes and increased by oxidative stress from mitochondrial dysfunction or inflammatory responses. We solved the crystal structures of Thermotoga maritima EndoV in complex with a hypoxanthine lesion substrate and with product DNA. The PYIP wedge motif acts as a minor groove-damage sensor for helical distortions and base mismatches and separates DNA strands at the lesion. EndoV incises DNA with an unusual offset nick 1 nucleotide 3' of the lesion, as the deaminated adenine is rotated approximately 90 degrees into a recognition pocket approximately 8 A from the catalytic site. Tight binding by the lesion-recognition pocket in addition to Mg(2+) and hydrogen-bonding interactions to the DNA ends stabilize the product complex, suggesting an orderly recruitment of downstream proteins in this base-repair pathway.
authors.affiliation: Centre for Molecular Biology and Neuroscience, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Dalhus
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Arvai
authors.forename: Ida
authors.initials: I
authors.lastname: Rosnes
authors.forename: Øyvind E
authors.initials: ØE
authors.lastname: Olsen
authors.forename: Paul H
authors.initials: PH
authors.lastname: Backe
authors.forename: Ingrun
authors.initials: I
authors.lastname: Alseth
authors.forename: Honghai
authors.initials: H
authors.lastname: Gao
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cao
authors.forename: John A
authors.initials: JA
authors.lastname: Tainer
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000737:chemistry* / Q000378:metabolism; D019271:Hypoxanthine / Q000378:metabolism; D008958:Models, Molecular; D020124:Thermotoga maritima / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D019271:Hypoxanthine; D004247:DNA; D043224:Deoxyribonuclease (Pyrimidine Dimer)