Structural highlights
Function
[MUG_ECOLI] Excises ethenocytosine and uracil, which can arise by alkylation or deamination of cytosine, respectively, from the corresponding mispairs with guanine in ds-DNA. It is capable of hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of the DNA and the mispaired base. The complementary strand guanine functions in substrate recognition. Required for DNA damage lesion repair in stationary-phase cells.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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, N(4)-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.
Crystal structure of a thwarted mismatch glycosylase DNA repair complex.,Barrett TE, Scharer OD, Savva R, Brown T, Jiricny J, Verdine GL, Pearl LH EMBO J. 1999 Dec 1;18(23):6599-609. PMID:10581234[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gallinari P, Jiricny J. A new class of uracil-DNA glycosylases related to human thymine-DNA glycosylase. Nature. 1996 Oct 24;383(6602):735-8. PMID:8878487 doi:http://dx.doi.org/10.1038/383735a0
- ↑ O'Neill RJ, Vorob'eva OV, Shahbakhti H, Zmuda E, Bhagwat AS, Baldwin GS. Mismatch uracil glycosylase from Escherichia coli: a general mismatch or a specific DNA glycosylase? J Biol Chem. 2003 Jun 6;278(23):20526-32. Epub 2003 Mar 31. PMID:12668677 doi:http://dx.doi.org/10.1074/jbc.M210860200
- ↑ Barrett TE, Scharer OD, Savva R, Brown T, Jiricny J, Verdine GL, Pearl LH. Crystal structure of a thwarted mismatch glycosylase DNA repair complex. EMBO J. 1999 Dec 1;18(23):6599-609. PMID:10581234 doi:10.1093/emboj/18.23.6599
