Taxonomic distribution of proteins containing UDG domains

The UDG domain within your query sequence starts at position 121 and ends at position 282, and its E-value is 5.86e-35.

The alpha/beta fold uracil DNA glycosylases: a common origin with diversefates.

Aravind L, Koonin EV
Genome Biol. 2000; 1: 7-7

BACKGROUND: Uracil DNA glycosylases (UDGs) are major repair enzymes thatprotect DNA from mutational damage caused by uracil incorporated as aresult of a polymerase error or deamination of cytosine. Four distinctfamilies of UDGs have been identified, which show very limited sequencesimilarity to each other, although two of them have been shown to possessthe same structural fold. The structural and evolutionary relationshipsbetween the rest of the UDGs remain uncertain. RESULTS: Using sequenceprofile searches, multiple alignment analysis and protein structurecomparisons, we show here that all known UDGs possess the same fold andmust have evolved from a common ancestor. Although all UDGs catalyzeessentially the same reaction, significant changes in the configuration ofthe catalytic residues were detected within their common fold, whichprobably results in differences in the biochemistry of these enzymes. Theextreme sequence divergence of the UDGs, which is unusual for enzymes withthe same principal activity, is probably due to the major role of theuracil-flipping caused by the conformational strain enacted by the enzymeon uracil-containing DNA, as compared with the catalytic action ofindividual polar residues. We predict two previously undetected familiesof UDGs and delineate a hypothetical scenario for their evolution.CONCLUSIONS: UDGs form a single protein superfamily with a distinctstructural fold and a common evolutionary origin. Differences in thecatalytic mechanism of the different families combined with theconstruction of the catalytic pocket have, however, resulted in extremesequence divergence of these enzymes.

Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatchrecognition by complementary-strand interactions.

Barrett TE, Savva R, Panayotou G, Barlow T, Brown T, Jiricny J, Pearl LH
Cell. 1998; 92: 117-29

G:U mismatches resulting from deamination of cytosine are the most commonpromutagenic lesions occurring in DNA. Uracil is removed in abase-excision repair pathway by uracil DNA-glycosylase (UDG), whichexcises uracil from both single- and double-stranded DNA. Recently, abiochemically distinct family of DNA repair enzymes has been identified,which excises both uracil and thymine, but only from mispairs withguanine. Crystal structures of the mismatch-specific uracilDNA-glycosylase (MUG) from E. coli, and of a DNA complex, reveal aremarkable structural and functional homology to UDGs despite low sequenceidentity. Details of the MUG structure explain its thymine DNA-glycosylaseactivity and the specificity for G:U/T mispairs, which derives from directrecognition of guanine on the complementary strand.