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- Title
Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8.
- Authors
Sugahara, Mitsuaki; Mikawa, Tsutomu; Kumasaka, Takashi; Yamamoto, Masaki; Kato, Ryuichi; Fukuyama, Keiichi; Inoue, Yorinao; Kuramitsu, Seiki
- Abstract
The MutM [formamidopyrimidine DNA glycosylase (Fpg)] protein is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidatively damaged bases (N-glycosylase activity) and cleaves both the 3′- and 5±-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity). The crystal structure of MutM from an extreme thermophilc, Thermus thermophilus HB8, was determined at 1.9 Å resolution with multiwavelength anomalous diffraction phasing using the intrinsic Zn2+ ion of the zinc finger. MutM is composed of two distinct and novel domains connected by a flexible hinge. There is a large, electrostatically positive cleft lined by highly conserved residues between the domains. On the basis of the three-dimensional structure and taking account of previous biochemical experiments, we propose a DNA-binding mode and reaction mechanism for MutM. The locations of the putative catalytic residues and the two DNA-binding motifs (the zinc finger and the helix-two-turns-helix motifs) suggest that the oxidized base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes.
- Subjects
ZINC-finger proteins; DNA damage; CARRIER proteins; PROTEINS; BINDING sites; BIOCHEMISTRY; MOLECULAR biology; CYTOLOGY
- Publication
EMBO Journal, 2000, Vol 19, Issue 15, p3857
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/19.15.3857