Crystal structure of (S)-3-O-geranylgeranylglyceryl phosphate synthase fromThermoplasma acidophilumin complex with the substratesn-glycerol 1-phosphate

Abstract

(S)-3-O-Geranylgeranylglyceryl phosphate synthase (GGGPS) catalyzes the initial ether-bond formation betweensn-glycerol 1-phosphate (G1P) and geranylgeranyl pyrophosphate to synthesize (S)-3-O-geranylgeranylglyceryl phosphate in the production of an archaeal cell-membrane lipid molecule. Archaeal GGGPS proteins are divided into two groups (group I and group II). In this study, the crystal structure of the archaeal group II GGGPS fromThermoplasma acidophilum(TaGGGPS) was determined at 2.35 Å resolution. The structure of TaGGGPS showed that it has a TIM-barrel fold, the third helix of which is disordered (α3*), and that it forms a homodimer, although a pre-existing structure of an archaeal group II GGGPS (fromMethanothermobacter thermautotrophicus) showed a hexameric form. The structure of TaGGGPS showed the precise G1P-recognition mechanism of an archaeal group II GGGPS. The structure of TaGGGPS and molecular-dynamics simulation analysis showed fluctuation of the β2–α2, α3* and α5a regions, which is predicted to be important for substrate uptake and/or product release by TaGGGPS.