Conformational changes of DNA repair glycosylase MutM triggered by DNA binding
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Neisseria meningitidis, DNA repair, Fpg/Nei, MutM, base excision DNA repair,
- MeSH
- Bacterial Proteins chemistry metabolism MeSH
- DNA, Bacterial chemistry metabolism MeSH
- DNA-Formamidopyrimidine Glycosylase chemistry metabolism MeSH
- Crystallography, X-Ray MeSH
- Neisseria meningitidis enzymology MeSH
- Protein Domains MeSH
- Protein Binding MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Bacterial Proteins MeSH
- DNA, Bacterial MeSH
- DNA-Formamidopyrimidine Glycosylase MeSH
Bacterial MutM is a DNA repair glycosylase removing DNA damage generated from oxidative stress and, therefore, preventing mutations and genomic instability. MutM belongs to the Fpg/Nei family of prokaryotic enzymes sharing structural and functional similarities with their eukaryotic counterparts, for example, NEIL1-NEIL3. Here, we present two crystal structures of MutM from pathogenic Neisseria meningitidis: a MutM holoenzyme and MutM bound to DNA. The free enzyme exists in an open conformation, while upon binding to DNA, both the enzyme and DNA undergo substantial structural changes and domain rearrangement. Our data show that not only NEI glycosylases but also the MutMs undergo dramatic conformational changes. Moreover, crystallographic data support the previously published observations that MutM enzymes are rather flexible and dynamic molecules.
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