The cytidylyltransferase superfamily: identification of the nucleotide-binding site and fold prediction.
The crystal structure of glycerol-3-phosphate cytidylyltransferase from B. subtilis (TagD) is about to be solved. Here, we report a testable structure prediction based on the identification by sequence analysis of a superfamily of functionally diverse but structurally similar nucleotide-binding enzymes. We predict that TagD is a member of this family. The most conserved region in this superfamily resembles the ATP-binding HiGH motif of class I aminoacyl-tRNA synthetases. The predicted secondary structure of cytidylyltransferase and its homologues is compatible with the alpha/beta topography of the class I aminoacyl-tRNA synthetases. The hypothesis of similarity of fold is strengthened by sequence-structure alignment and 3D model building using the known structure of tyrosyl tRNA synthetase as template. The proposed 3D model of TagD is plausible both structurally, with a well packed hydrophobic core, and functionally, as the most conserved residues cluster around the putative nucleotide binding site. If correct, the model would imply a very ancient evolutionary link between class I tRNA synthetases and the novel cytidylyltransferase superfamily.
D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry; D001412:Bacillus subtilis / Q000201:enzymology*; D001665:Binding Sites; D005075:Biological Evolution; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017421:Sequence Analysis
D009711:Nucleotides; D009713:Nucleotidyltransferases; C020675:glycerol-3-phosphate cytidylyltransferase; D000604:Amino Acyl-tRNA Synthetases