The C-terminal domain of HPII catalase is a member of the type I glutamine amidotransferase superfamily.
Discovering distant evolutionary relationships between proteins requires detecting subtle similarities. Here we use a combination of sequence and structure analysis to show that the C-terminal domain of Escherichia coli HPII catalase with available spatial structure is a divergent member of the type I glutamine amidotransferase (GAT) superfamily. GAT-containing proteins include many biosynthetic enzymes such as E. coli carbamoyl phosphate synthetase and anthranilate synthase. Typical GAT domains have Rossmann fold-like topology and possess a catalytic triad similar to that of proteases. The C-terminal domain of HPII catalase has the GAT Rossmann fold but lacks the triad and therefore loses enzymatic activity. In addition, we detect significant sequence similarity between thiJ domains, some of which are known to have protease activity, and typical GAT proteins. Evolutionary tree analysis of the entire GAT superfamily indicates that the HPII catalase is more closely related to thiJ domains than to classical GAT domains and is likely to have evolved from a thiJ-like protein. This work illustrates the strength of sequence-based profile analysis techniques coupled with structural superpositions in developing an evolutionarily relevant classification of protein structures. Proteins 2001;42:230-236.
Horvath
M M
MM
Biochemistry Department, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA.
Grishin
N V
NV
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000878:Anthranilate Synthase; D002374:Catalase / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology; D008969:Molecular Sequence Data; D019884:Nitrogenous Group Transferases / Q000737:chemistry; D010802:Phylogeny; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
C102664:hydroperoxidase II; D002374:Catalase; D019884:Nitrogenous Group Transferases; D000878:Anthranilate Synthase; C020655:anthranilate synthase, glutamine amidotransferase subunit