Hexameric assembly of the bifunctional methylerythritol 2,4-cyclodiphosphate synthase and protein-protein associations in the deoxy-xylulose-dependent pathway of isoprenoid precursor biosynthesis.
The bifunctional methylerythritol 4-phosphate cytidylyltransferase methylerythritol 2,4-cyclodiphosphate synthase (IspDF) is unusual in that it catalyzes nonconsecutive reactions in the 1-deoxy-D-xylulose 5-phosphate (DOXP) pathway of isoprenoid precursor biosynthesis. The crystal structure of IspDF from the bacterial pathogen Campylobacter jejuni reveals an elongated hexamer with D3 symmetry compatible with the dimeric 2C-methyl-D-erythritol-4-phosphate cytidylyltransferase and trimeric 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase monofunctional enzymes. Complex formation of IspDF with 4-diphosphocytidyl-2C-methyl-D-erythritol kinase (IspE), the intervening enzyme activity in the pathway, has been observed in solution for the enzymes from C. jejuni and Agrobacterium tumefaciens. The monofunctional enzymes (2C-methyl-D-erythritol-4-phosphate cytidylyltransferase, IspE, and 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase) involved in the DOXP biosynthetic pathway of Escherichia coli also show physical associations. We propose that complex formation of the three enzymes at the core of the DOXP pathway can produce an assembly localizing 18 catalytic centers for the early stages of isoprenoid biosynthesis.
Gabrielsen
Mads
M
Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom.
Bond
Charles S
CS
Hallyburton
Irene
I
Hecht
Stefan
S
Bacher
Adelbert
A
Eisenreich
Wolfgang
W
Rohdich
Felix
F
Hunter
William N
WN
D000595:Amino Acid Sequence; D001483:Base Sequence; D016123:Campylobacter jejuni / Q000201:enzymology / Q000235:genetics; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid; D013729:Terpenes / Q000378:metabolism*; D014996:Xylulose / Q000031:analogs & derivatives* / Q000378:metabolism*
D004269:DNA, Bacterial; D021122:Protein Subunits; D013729:Terpenes; D014996:Xylulose; C029724:1-deoxy-2-pentulose; D019761:Phosphorus-Oxygen Lyases