Nature Structural Biology
5, 1058 - 1064 (1998)
doi:10.1038/4168
MutY catalytic core, mutant and bound adenine structures define specificity
for DNA repair enzyme superfamilyYue Guan1, 2, Raymond C. Manuel1, 3, Andrew S. Arvai1, 2, Sudip S. Parikh1, 2, Clifford D. Mol2, Jeffrey H. Miller4, R. Stephen Lloyd3
& John A. Tainer21
These authors contributed equally to this work. 2
Department of Molecular Biology, Skaggs Institute for
Chemical Biology, The Scripps Research Institute, MB4, 10550
North Torrey Pines Rd., La Jolla, California 92037, USA. 3
Sealy Center for Molecular Science, University of Texas
Medical Branch, 301 University Blvd., Galveston, Texas 77555, USA. 4
Department of Microbiology and Molecular Genetics,
Molecular Biology Institute, UCLA, Los Angeles, California 90095, USA.
Correspondence should be addressed to John A. Tainer jat@scripps.edu
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.
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