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. (C) 1995 Wiley-Liss, Inc.