TY - JOUR
T1 - Structure of formamidopyrimidine-DNA glycosylase covalently complexed to DNA
AU - Gilboa, Rotem
AU - Zharkov, Dmitry O.
AU - Golan, Gali
AU - Fernandes, Andrea S.
AU - Gerchman, Sue Ellen
AU - Matz, Eileen
AU - Kycia, Jadwiga H.
AU - Grollman, Arthur P.
AU - Shoham, Gil
PY - 2002/5/31
Y1 - 2002/5/31
N2 - Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines from damaged DNA. The Schiff base intermediate formed during this reaction between Escherichia coli Fpg and DNA was trapped by reduction with sodium borohydride, and the structure of the resulting covalently cross-linked complex was determined at a 2.1-A resolution. Fpg is a bilobal protein with a wide, positively charged DNA-binding groove. It possesses a conserved zinc finger and a helix-two turn-helix motif that participate in DNA binding. The absolutely conserved residues Lys-56, His-70, Asn-168, and Arg-258 form hydrogen bonds to the phosphodiester backbone of DNA, which is sharply kinked at the lesion site. Residues Met-73, Arg109, and Phe-110 are inserted into the DNA helix, filling the void created by nucleotide eversion. A deep hydrophobic pocket in the active site is positioned to accommodate an everted base. Structural analysis of the Fpg DNA complex reveals essential features of damage recognition and the catalytic mechanism of Fpg.
AB - Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines from damaged DNA. The Schiff base intermediate formed during this reaction between Escherichia coli Fpg and DNA was trapped by reduction with sodium borohydride, and the structure of the resulting covalently cross-linked complex was determined at a 2.1-A resolution. Fpg is a bilobal protein with a wide, positively charged DNA-binding groove. It possesses a conserved zinc finger and a helix-two turn-helix motif that participate in DNA binding. The absolutely conserved residues Lys-56, His-70, Asn-168, and Arg-258 form hydrogen bonds to the phosphodiester backbone of DNA, which is sharply kinked at the lesion site. Residues Met-73, Arg109, and Phe-110 are inserted into the DNA helix, filling the void created by nucleotide eversion. A deep hydrophobic pocket in the active site is positioned to accommodate an everted base. Structural analysis of the Fpg DNA complex reveals essential features of damage recognition and the catalytic mechanism of Fpg.
UR - http://www.scopus.com/inward/record.url?scp=0037205477&partnerID=8YFLogxK
U2 - 10.1074/jbc.M202058200
DO - 10.1074/jbc.M202058200
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C2 - 11912217
AN - SCOPUS:0037205477
SN - 0021-9258
VL - 277
SP - 19811
EP - 19816
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 22
ER -