The crystal structure of a plant 2C-methyl-D-erythritol 4-phosphate cytidylyltransferase exhibits a distinct quaternary structure compared to bacterial homologues and a possible role in feedback regulation for cytidine monophosphate.
The homodimeric 2C-methyl-D-erythritol 4-phosphate cytidylyltransferase contributes to the nonmevalonate pathway of isoprenoid biosynthesis. The crystal structure of the catalytic domain of the recombinant enzyme derived from the plant Arabidopsis thaliana has been solved by molecular replacement and refined to 2.0 A resolution. The structure contains cytidine monophosphate bound in the active site, a ligand that has been acquired from the bacterial expression system, and this observation suggests a mechanism for feedback regulation of enzyme activity. Comparisons with bacterial enzyme structures, in particular the enzyme from Escherichia coli, indicate that whilst individual subunits overlay well, the arrangement of subunits in each functional dimer is different. That distinct quaternary structures are available, in conjunction with the observation that the protein structure contains localized areas of disorder, suggests that conformational flexibility may contribute to the function of this enzyme.
Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, UK.
Mads
M
Gabrielsen
Johannes
J
Kaiser
Felix
F
Rohdich
Wolfgang
W
Eisenreich
Ralf
R
Laupitz
Adelbert
A
Bacher
Charles S
CS
Bond
William N
WN
Hunter
D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003568:Cytidine Monophosphate / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D005246:Feedback; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017386:Sequence Homology, Amino Acid
C435808:2-C-methyl erythritol 4-phosphate cytidylyltransferase; D009713:Nucleotidyltransferases; D003568:Cytidine Monophosphate