The crystal structure of (S)-3-O-geranylgeranylglyceryl phosphate synthase reveals an ancient fold for an ancient enzyme.
We report crystal structures of the citrate and sn-glycerol-1-phosphate (G1P) complexes of (S)-3-O-geranylgeranylglyceryl phosphate synthase from Archaeoglobus fulgidus (AfGGGPS) at 1.55 and 2.0 A resolution, respectively. AfGGGPS is an enzyme that performs the committed step in archaeal lipid biosynthesis, and it presents the first triose phosphate isomerase (TIM)-barrel structure with a prenyltransferase function. Our studies provide insight into the catalytic mechanism of AfGGGPS and demonstrate how it selects for the sn-G1P isomer. The replacement of "Helix 3" by a "strand" in AfGGGPS, a novel modification to the canonical TIM-barrel fold, suggests a model of enzyme adaptation that involves a "greasy slide" and a "swinging door." We propose functions for the homologous PcrB proteins, which are conserved in a subset of pathogenic bacteria, as either prenyltransferases or being involved in lipoteichoic acid biosynthesis. Sequence and structural comparisons lead us to postulate an early evolutionary history for AfGGGPS, which may highlight its role in the emergence of Archaea.
Payandeh
Jian
J
Departmentsof Medical Biophysics, University of Toronto, Division of Cancer Genomics & Proteomics, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada.
Fujihashi
Masahiro
M
Gillon
Wanda
W
Pai
Emil F
EF
D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019611:Archaeoglobus fulgidus / Q000201:enzymology*; D019343:Citric Acid / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005994:Glycerophosphates / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D019843:Archaeal Proteins; D005994:Glycerophosphates; D019343:Citric Acid; C029620:alpha-glycerophosphoric acid; D019883:Alkyl and Aryl Transferases; C083737:phosphoglycerol geranylgeranyltransferase