THE PREDICTED SECONDARY STRUCTURE OF THE G-TYPE GLUTAMINE AMIDOTRANSFERASE IS COMPATIBLE WITH TIM-BARREL TOPOLOGY

Glutamine amidotransferase (GAT) subunits or domains catalyze an impor tant partial reaction in many complex biosynthetic reactions. The stru cture of one member of the F-type GATs is known, but the structure of the unrelated G-type is still unknown, Because many protein sequences are available for anthranilate synthase component II (product of the t rpG gene), we have predicted its average secondary structure by a join t prediction method [Niermann and Kirschner (1991a) Protein Engng, 4, 359-370], The predicted eight beta-strands and seven alpha-helices fol low an 8-fold cyclic repetition of a beta-strand-loop-alpha-helix-loop module with helix alpha(7) missing. This pattern of secondary structu re suggests that the G-type GAT domain has an 8-fold beta alpha-barrel topology, as found first in triose phosphate isomerase (TIM-barrel). This model is supported by the location of known catalytically essenti al residues in loops between beta-strands and alpha-helices. Evidence from published sequencing and mutational studies on selected members o f the GAT superfamily (carbamoyl phosphate, imidazoleglycerol phosphat e, GMP and CTP synthases) support both the secondary structure predict ion and the TIM-barrel topology.