MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily

Y. Guan, R. C. Manuel, A. S. Arvai, S. S. Parikh, C. D. Mol, J. H. Miller, Robert (Stephen) Lloyd, J. A. Tainer

Research output: Contribution to journalArticle

274 Citations (Scopus)

Abstract

The DNA glycosylase MutY, which is a member of the Helix-hairpin-Helix (HhH) DNA glycosylase superfamily, excises adenine from mispairs with 8- oxoguanine and guanine. High-resolution crystal structures of the MutY catalytic core (cMutY), the complex with bound adenine, and designed mutants reveal the basis for adenine specificity and glycosyl bond cleavage chemistry. The two cMutY helical domains form a positively-charged groove with the adenine-specific pocket at their interface. The Watson-Crick hydrogen bond partners of the bound adenine are substituted by protein atoms, confirming a nucleotide flipping mechanism, and supporting a specific DNA binding orientation by MutY and structurally related DNA glycosylases.

Original languageEnglish (US)
Pages (from-to)1058-1064
Number of pages7
JournalNature Structural Biology
Volume5
Issue number12
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

DNA Repair Enzymes
Adenine
Catalytic Domain
DNA Glycosylases
Guanine
Hydrogen
Hydrogen bonds
Nucleotides
Crystal structure
Atoms
DNA
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Guan, Y., Manuel, R. C., Arvai, A. S., Parikh, S. S., Mol, C. D., Miller, J. H., ... Tainer, J. A. (1998). MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily. Nature Structural Biology, 5(12), 1058-1064. https://doi.org/10.1038/4168

MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily. / Guan, Y.; Manuel, R. C.; Arvai, A. S.; Parikh, S. S.; Mol, C. D.; Miller, J. H.; Lloyd, Robert (Stephen); Tainer, J. A.

In: Nature Structural Biology, Vol. 5, No. 12, 1998, p. 1058-1064.

Research output: Contribution to journalArticle

Guan, Y, Manuel, RC, Arvai, AS, Parikh, SS, Mol, CD, Miller, JH, Lloyd, RS & Tainer, JA 1998, 'MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily', Nature Structural Biology, vol. 5, no. 12, pp. 1058-1064. https://doi.org/10.1038/4168
Guan, Y. ; Manuel, R. C. ; Arvai, A. S. ; Parikh, S. S. ; Mol, C. D. ; Miller, J. H. ; Lloyd, Robert (Stephen) ; Tainer, J. A. / MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily. In: Nature Structural Biology. 1998 ; Vol. 5, No. 12. pp. 1058-1064.
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