title: Crystallographic and functional studies of very short patch repair endonuclease.
abstract: Vsr endonuclease plays a crucial role in the repair of TG mismatched base pairs, which are generated by the spontaneous degradation of methylated cytidines; Vsr recognizes the mismatched base pair and cleaves the phosphate backbone 5' to the thymidine. We have determined the crystal structure of a truncated form of this endonuclease at 1.8 A resolution. The protein contains one structural zinc-binding module. Unexpectedly, its overall topology resembles members of the type II restriction endonuclease family. Subsequent mutational and biochemical analyses showed that certain elements in the catalytic site are also conserved. However, the identification of a critical histidine and evidence of an active site metal-binding coordination that is novel to endonucleases indicate a distinct catalytic mechanism.
authors.affiliation: Department of Structural Biology, Biomolecular Engineering Research Institute (BERI), Osaka, Japan.
authors.forename: S E
authors.initials: SE
authors.lastname: Tsutakawa
authors.forename: T
authors.initials: T
authors.lastname: Muto
authors.forename: T
authors.initials: T
authors.lastname: Kawate
authors.forename: H
authors.initials: H
authors.lastname: Jingami
authors.forename: N
authors.initials: N
authors.lastname: Kunishima
authors.forename: M
authors.initials: M
authors.lastname: Ariyoshi
authors.forename: D
authors.initials: D
authors.lastname: Kohda
authors.forename: M
authors.initials: M
authors.lastname: Nakagawa
authors.forename: K
authors.initials: K
authors.lastname: Morikawa
mesh_terms: D000409:Alanine; D020137:Base Pair Mismatch; D020134:Catalytic Domain; D017124:Conserved Sequence; D003461:Crystallography; D004260:DNA Repair; D015252:Deoxyribonucleases, Type II Site-Specific / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D008345:Manganese; D004706:Endodeoxyribonucleases; C071421:vsr endonuclease; D015252:Deoxyribonucleases, Type II Site-Specific; D000409:Alanine