MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily.
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.
Guan
Y
Y
Department of Molecular Biology, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Manuel
R C
RC
Arvai
A S
AS
Parikh
S S
SS
Mol
C D
CD
Miller
J H
JH
Lloyd
S
S
Tainer
J A
JA
D000225:Adenine / Q000378:metabolism*; D000595:Amino Acid Sequence; D020137:Base Pair Mismatch; D020134:Catalytic Domain / Q000235:genetics; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D045647:DNA Glycosylases; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009699:N-Glycosyl Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D013379:Substrate Specificity
C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D000225:Adenine