Structural highlights
Function
GGGPS_THEAC Prenyltransferase that catalyzes the transfer of the geranylgeranyl moiety of geranylgeranyl diphosphate (GGPP) to the C3 hydroxyl of sn-glycerol-1-phosphate (G1P). This reaction is the first ether-bond-formation step in the biosynthesis of archaeal membrane lipids. Cannot use sn-glycerol-3-phosphate (G3P) as substrate.[1] [2]
Publication Abstract from PubMed
(S)-3-O-Geranylgeranylglyceryl phosphate synthase (GGGPS) catalyzes the initial ether-bond formation between sn-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 from Thermoplasma acidophilum (TaGGGPS) was determined at 2.35 A resolution. The structure of TaGGGPS showed that it has a TIM-barrel fold, the third helix of which is disordered (alpha3*), and that it forms a homodimer, although a pre-existing structure of an archaeal group II GGGPS (from Methanothermobacter 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 beta2-alpha2, alpha3* and alpha5a regions, which is predicted to be important for substrate uptake and/or product release by TaGGGPS.
Crystal structure of (S)-3-O-geranylgeranylglyceryl phosphate synthase from Thermoplasma acidophilum in complex with the substrate sn-glycerol 1-phosphate.,Nemoto N, Miyazono KI, Tanokura M, Yamagishi A Acta Crystallogr F Struct Biol Commun. 2019 Jul 1;75(Pt 7):470-479. doi:, 10.1107/S2053230X19007453. Epub 2019 Jun 17. PMID:31282866[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nemoto N, Oshima T, Yamagishi A. Purification and characterization of geranylgeranylglyceryl phosphate synthase from a thermoacidophilic archaeon, Thermoplasma acidophilum. J Biochem. 2003 May;133(5):651-7. PMID:12801917
- ↑ Peterhoff D, Beer B, Rajendran C, Kumpula EP, Kapetaniou E, Guldan H, Wierenga RK, Sterner R, Babinger P. A comprehensive analysis of the geranylgeranylglyceryl phosphate synthase enzyme family identifies novel members and reveals mechanisms of substrate specificity and quaternary structure organization. Mol Microbiol. 2014 May;92(4):885-99. doi: 10.1111/mmi.12596. Epub 2014 Apr 16. PMID:24684232 doi:http://dx.doi.org/10.1111/mmi.12596
- ↑ Nemoto N, Miyazono KI, Tanokura M, Yamagishi A. Crystal structure of (S)-3-O-geranylgeranylglyceryl phosphate synthase from Thermoplasma acidophilum in complex with the substrate sn-glycerol 1-phosphate. Acta Crystallogr F Struct Biol Commun. 2019 Jul 1;75(Pt 7):470-479. doi:, 10.1107/S2053230X19007453. Epub 2019 Jun 17. PMID:31282866 doi:http://dx.doi.org/10.1107/S2053230X19007453
