BIROn - Birkbeck Institutional Research Online

    Crystal structure of a thwarted mismatch glycosylase DNA repair complex

    Barrett, T.E. and Schärer, O.D. and Savva, Renos and Brown, T. and Jiricny, J. and Verdine, G.L. and Pearl, L.H. (1999) Crystal structure of a thwarted mismatch glycosylase DNA repair complex. Embo Journal 18 (23), pp. 6599-6609. ISSN 0261-4189.

    Full text not available from this repository.

    Abstract

    The bacterial mismatch‐specific uracil‐DNA glycosylase (MUG) and eukaryotic thymine‐DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base‐excision repair of G:U/T mismatches. Despite low sequence homology, the MUG/TDG enzymes are structurally related to the uracil‐DNA glycosylase enzymes, but have a very different mechanism for substrate recognition. We have now determined the crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non‐hydrolysable deoxyuridine analogue mismatched with guanine, providing the first structure of an intact substrate‐nucleotide productively bound to a hydrolytic DNA glycosylase. The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non‐specific pyrimidine‐binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3,N4‐ethenocytosine. Together with structures for the free enzyme and for an abasic‐DNA product complex, the MUG–substrate analogue complex reveals the conformational changes accompanying the catalytic cycle of substrate binding, base excision and product release.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Innovation Management Research, Birkbeck Centre for
    Depositing User: Sarah Hall
    Date Deposited: 14 May 2019 11:13
    Last Modified: 02 Aug 2023 17:51
    URI: https://eprints.bbk.ac.uk/id/eprint/27523

    Statistics

    Activity Overview
    6 month trend
    0Downloads
    6 month trend
    271Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item