8RUW

Crystal structure of Archaeoglobus fulgidus (S)-3-O-geranylgeranylglyceryl phosphate synthase

Summary for 8RUW

• Entry DOI: 10.2210/pdb8ruw/pdb
• Descriptor: Geranylgeranylglyceryl phosphate synthase, PHOSPHATE ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: gggps, transferase
• Biological source: Archaeoglobus fulgidus DSM 4304
• Total number of polymer chains: 6
• Total formula weight: 171493.36

Authors

Eilert, L.,Blankenfeldt, W. (deposition date: 2024-01-31, release date: 2024-10-16, Last modification date: 2024-11-13)

Primary citation

Kaspar, F.,Eilert, L.,Staar, S.,Oung, S.W.,Wolter, M.,Ganskow, C.S.G.,Kemper, S.,Klahn, P.,Jacob, C.R.,Blankenfeldt, W.,Schallmey, A.
Biocatalytic Ether Lipid Synthesis by an Archaeal Glycerolprenylase.
Angew.Chem.Int.Ed.Engl., 63:e202412597-e202412597, 2024

PubMed Abstract: Although ethers are common in secondary natural products, they are an underrepresented functional group in primary metabolism. As such, there are comparably few enzymes capable of constructing ether bonds in a general fashion. However, such enzymes are highly sought after for synthetic applications as they typically operate with higher regioselectivity and under milder conditions than traditional organochemical approaches. To expand the repertoire of well characterized ether synthases, we herein report on a promiscuous archaeal prenyltransferase from the scarcely researched family of geranylgeranylglyceryl phosphate synthases (GGGPSs or GPSs). We show that the ultrastable Archaeoglobus fulgidus GPS makes various (E)- and (Z)-configured prenyl glycerol ethers from the corresponding pyrophosphates while exerting perfect control over the configuration at the glycerol unit. Based on experimental and computational data, we propose a mechanism for this enzyme which involves an intermediary prenyl carbocation equivalent. As such, this study provides the fundamental understanding and methods to introduce GPSs into the biocatalytic alkylation toolbox.

PubMed: 39359010
DOI: 10.1002/anie.202412597

Experimental method

X-RAY DIFFRACTION (2.48 Å)