%0 Journal Article
%T The alpha/beta fold uracil DNA glycosylases: a common origin with diverse fates
%A L Aravind
%A Eugene V Koonin
%J Genome Biology
%D 2000
%I BioMed Central
%R 10.1186/gb-2000-1-4-research0007
%X Using sequence profile searches, multiple alignment analysis and protein structure comparisons, we show here that all known UDGs possess the same fold and must have evolved from a common ancestor. Although all UDGs catalyze essentially the same reaction, significant changes in the configuration of the catalytic residues were detected within their common fold, which probably results in differences in the biochemistry of these enzymes. The extreme sequence divergence of the UDGs, which is unusual for enzymes with the same principal activity, is probably due to the major role of the uracil-flipping caused by the conformational strain enacted by the enzyme on uracil-containing DNA, as compared with the catalytic action of individual polar residues. We predict two previously undetected families of UDGs and delineate a hypothetical scenario for their evolution.UDGs form a single protein superfamily with a distinct structural fold and a common evolutionary origin. Differences in the catalytic mechanism of the different families combined with the construction of the catalytic pocket have, however, resulted in extreme sequence divergence of these enzymes.Mutagenic uracil appears in DNA opposite to guanine as a result of misincorporation or of deamination of cytosine. Similarly, the deamination process generates thymine opposite guanine in those organisms that undergo cytosine methylation [1,2]. DNA is safeguarded from the consequences of these events by the activity of uracil DNA glycosylases (UDGs), which remove uracil (and sometimes thymine) from the sugar backbone of DNA without breaking the phosphodiester bonds in the backbone. There are different types of these enzymes in the three superkingdoms of life. The best studied family of UDGs, typified by the Escherichia coli Ung protein, is largely specific for uracil and is present in a variety of bacteria, eukaryotes and large eukaryotic DNA viruses [1,3,4]. The mismatch-specific uracil DNA glycosylases (MUGs) have been ide
%U http://genomebiology.com/2000/1/4/research/0007