| Abstract
| - We used freeze trapping to stabilize the Michaelis complex of wild-type tryptophan synthaseand the α-subunit substrate indole-3-glycerol phosphate (IGP) and determined its structure to 1.8 Åresolution. In addition, we determined the 1.4 Å resolution structure of the complex with indole-3-propanolephosphate (IPP), a noncleavable IGP analogue. The interaction of the 3‘-hydroxyl of IGP with the catalyticαGlu49 leads to a twisting of the propane chain and to a repositioning of the indole ring compared toIPP. Concomitantly, the catalytic αAsp60 rotates resulting in a translocation of the COMM domain[βGly102-βGly189, for definition see Schneider et al. (1998) Biochemistry37, 5394−5406] in a directionopposite to the one in the IPP complex. This results in loss of the allosteric sodium ion bound at theβ-subunit and an opening of the β-active site, thereby making the cofactor pyridoxal 5‘-phosphate (PLP)accessible to solvent and thus serine binding. These findings form the structural basis for the informationtransfer from the α- to the β-subunit and may explain the affinity increase of the β-active site for serineupon IGP binding.
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