Crystal Structure of Wild-Type Tryptophan Synthase Complexed with the Natural Substrate Indole-3-glycerol Phosphate
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- 作者：Michael Weyand and Ilme Schlichting
- 刊名：Biochemistry
- 出版年：1999
- 出版时间：December 14, 1999
- 年：1999
- 卷：38
- 期：50
- 页码：16469 - 16480
- 全文大小：1132K
- 年卷期：v.38,no.50(December 14, 1999)
- ISSN：1520-4995
文摘
We used freeze trapping to stabilize the Michaelis complex of wild-type tryptophan synthaseand the 
-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 catalyticGlu49 leads to a twisting of the propane chain and to a repositioning of the indole ring compared toIPP. Concomitantly, the catalytic Asp60 rotates resulting in a translocation of the COMM domain[
Gly102-Gly189, for definition see Schneider et al. (1998) Biochemistry 37, 5394-5406] in a directionopposite to the one in the IPP complex. This results in loss of the allosteric sodium ion bound at the-subunit and an opening of the -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 - to the -subunit and may explain the affinity increase of the -active site for serineupon IGP binding.
-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 catalyticGlu49 leads to a twisting of the propane chain and to a repositioning of the indole ring compared toIPP. Concomitantly, the catalytic Asp60 rotates resulting in a translocation of the COMM domain[Gly102-Gly189, for definition see Schneider et al. (1998) Biochemistry 37, 5394-5406] in a directionopposite to the one in the IPP complex. This results in loss of the allosteric sodium ion bound at the-subunit and an opening of the -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 - to the -subunit and may explain the affinity increase of the -active site for serineupon IGP binding.