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 aminoacyI‐tRNA synthetases. The predicted secondary structure of cytidylyltransferase and its homologues is compatible with the α/β 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. © 1995 Wiley‐Liss, Inc.

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