Three-Dimensional Structure of a DNA Repair Enzyme, 3-Methyladenine DNA Glycosylase II, from Escherichia coli

Yamagata, Yuriko; Kato, Masato; Odawara, Kyoko; Tokuno, Y.; Nakashima, Yoko; Matsushima, Nobuko; Yasumura, K.; Tomita, Ken; Ihara, Kenji; Fujii, Youichi; Nakabeppu, Yusaku; Sekiguchi, Mutsuo; Fujii, Susumu

doi:10.1016/s0092-8674(00)80102-6

Cited by 139 publications

(133 citation statements)

References 55 publications

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“…Its surface has a prominent cleft lined with electron-rich aromatic residues that may guide an extrahelical, positively charged, alkylated base into a position where it may be subject to nucleophilic attack by water deprotonated by an Asp residue. AlkA is a compact globular protein consisting of 13 α-helices and a five-stranded anti-parallel β-sheet [158,159]. The structure consists of three roughly equal-sized domains (Figure 7).…”

Section: Three-dimensional Structure Of Alkamentioning

confidence: 99%

DNA glycosylases in the base excision repair of DNA

Krokan

Standal

Slupphaug

1997

Biochemical Journal

771

566

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A wide range of cytotoxic and mutagenic DNA bases are removed by different DNA glycosylases, which initiate the base excision repair pathway. DNA glycosylases cleave the Nglycosylic bond between the target base and deoxyribose, thus releasing a free base and leaving an apurinic\apyrimidinic (AP) site. In addition, several DNA glycosylases are bifunctional, since they also display a lyase activity that cleaves the phosphodiester backbone 3h to the AP site generated by the glycosylase activity. Structural data and sequence comparisons have identified common features among many of the DNA glycosylases. Their active sites have a structure that can only bind extrahelical target bases, as observed in the crystal structure of human uracil-DNA glycosylase in a complex with double-stranded DNA. Nucleotide flipping is apparently actively facilitated by the enzyme. With bacteriophage T4 endonuclease V, a pyrimidine-

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Section: Three-dimensional Structure Of Alkamentioning

confidence: 99%

DNA glycosylases in the base excision repair of DNA

Krokan

Standal

Slupphaug

1997

Biochemical Journal

771

566

View full text Add to dashboard Cite

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“…The 3-D structure of AlkA is available and has clarified the catalytic properties of the enzyme (Labahn et al, 1996;Yamagata et al, 1996). A comprehensive review (Hollis et al, 2000) describes the main structural features of AlkA.…”

Section: Methylating Agentsmentioning

confidence: 99%

Recent progress on the Ada response for inducible repair of DNA alkylation damage

2002

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“…There are now numerous examples of enzymes that repair or methylate DNA that act via base-flipping mechanisms (34 -36). These include HhaI and HaeIII methyltransferases (37,38), T4 endonuclease V (39,40), uracil DNA glycosylase (41, 42), 3-methyladenine DNA glycosylase II (43,44), and DNA photolyase (45). Several authors have suggested that alkyltransferase follows a similar general mechanism (34,36,46,47), and the crystal structure of the Ada-C protein would be consistent with such a model, in which the methylated base is flipped out of the DNA structure and rotated into a binding pocket in the protein (6,7).…”

Section: Repair Of O 6 -Benzylguaninementioning

confidence: 99%

Repair of O6-Benzylguanine by the Escherichia coli Ada and Ogt and the Human O6-Alkylguanine-DNA Alkyltransferases

Goodtzova

Kanugula

Edara

et al. 1997

Journal of Biological Chemistry

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O 6 -Methylguanine is removed from DNA via the transfer of the methyl group to a cysteine acceptor site present in the DNA repair protein O 6 -alkylguanine-DNA alkyltransferase. The human alkyltransferase is inactivated by the free base O 6 -benzylguanine, raising the possibility that substantially larger alkyl groups could also be accepted as substrates. However, the Escherichia coli alkyltransferase, Ada-C, is not inactivated by O 6 -benzylguanine. The Ada-C protein was rendered capable of reaction by the incorporation of two sitedirected mutations converting Ala 316 to a proline (A316P) and Trp 336 to alanine (W336A) or glycine (W336G). These changes increase the space at the active site of the protein where Cys 321 is buried and thus permit access of the O 6 -benzylguanine inhibitor. Reaction of the mutant A316P/W336A-Ada-C with O 6 -benzylguanine was greatly stimulated by the presence of DNA, providing strong support for the concept that binding of DNA to the Ada-C protein activates the protein. The Ada-C protein was able to repair O 6 -benzylguanine in a 16-mer oligodeoxyribonucleotide. However, the rate of repair was very slow, whereas the E. coli Ogt, the human alkyltransferase, and the mutant A316P/W336A-Ada-C alkyltransferases reacted very rapidly with this 16-mer substrate and preferentially repaired it when incubated with a mixture of the methylated and benzylated 16-mers. These results show that benzyl groups are better substrates than methyl groups for alkyltransferases provided that steric factors do not prevent binding of the substrate in the correct orientation for alkyl group transfer.

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Three-Dimensional Structure of a DNA Repair Enzyme, 3-Methyladenine DNA Glycosylase II, from Escherichia coli

Cited by 139 publications

References 55 publications

DNA glycosylases in the base excision repair of DNA

DNA glycosylases in the base excision repair of DNA

Recent progress on the Ada response for inducible repair of DNA alkylation damage

Repair of O6-Benzylguanine by the Escherichia coli Ada and Ogt and the Human O6-Alkylguanine-DNA Alkyltransferases

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