A possible nucleotide-binding domain in the tertiary fold of phosphoribosyltransferases.

Comparison of the primary structures of three phosphoribosyltransferases (human hypoxanthine-guanine, Salmonella typhimurium ATP, and Escherichia coli glutamine) showed no significant amino acid sequence homology except for a 35-residue span in hypoxanthine-guanine and glutamine phosphoribosyltransferases. However, comparison of smoothed plots of amino acid physical characteristics thought to control protein folding with amino acid sequence number resulted in a substantial correlation for a 120-residue stretch in each of the phosphoribosyltransferases. A secondary structure prediction analysis of the regions indicated a dinucleotide-binding fold with its characteristic beta alpha beta secondary structural pattern. Furthermore, the physical parametric correlation analysis suggested a common catalytic domain fold for hypoxanthine-guanine and glutamine phosphoribosyltransferases which was consistent with the register of the sequence homology. A possible binding mode of the phosphoribosyltransferase substrates is discussed. The physical parametric approach to protein sequence comparison may be generally applicable for distantly related proteins which maintain similar structural folds without any apparent sequence homology.