Crystal structure of wild-type tryptophan synthase complexed with the natural substrate indole-3-glycerol phosphate

We used freeze trapping to stabilize the Michaelis complex of wild-type try ptophan synthase and the alpha-subunit substrate indole-3-glycerol phosphat e (TGP) and determined its structure to 1.8 Angstrom resolution. In additio n, we determined the 1.4 Angstrom resolution structure of the complex with indole-3-propanole phosphate (IPP), a noncleavable IGP analogue. The intera ction of the 3'-hydroxyl of IGP with the catalytic alpha Glu49 leads to a t wisting of the propane chain and to a repositioning of the indole ring comp ared to IPP. Concomitantly, the catalytic ccAsp60 rotates resulting in a tr anslocation of the COMM domain [beta Gly102-beta Gly189, for definition see Schneider ct al. (1998) Biochemistry 37, 5394-5406] in a direction opposit e to the one in the IPP complex. This results in loss of the allosteric sod ium ion bound at the beta-subunit and an opening of the beta-active site, t hereby making the cofactor pyridoxal 5'-phosphate (PLP) accessible to solve nt and thus serine binding. These findings form the structural basis for th e information transfer from the alpha- to the beta-subunit and may explain the affinity increase of the beta-active site for serine upon IGP binding.