Crystal structure of dTDP-4-keto-6-deoxy-D-hexulose 3,5-epimerase from Methanobacterium thermoautotrophicum complexed with dTDP.
Deoxythymidine diphosphate (dTDP)-4-keto-6-deoxy-d-hexulose 3, 5-epimerase (RmlC) is involved in the biosynthesis of dTDP-l-rhamnose, which is an essential component of the bacterial cell wall. The crystal structure of RmlC from Methanobacterium thermoautotrophicum was determined in the presence and absence of dTDP, a substrate analogue. RmlC is a homodimer comprising a central jelly roll motif, which extends in two directions into longer beta-sheets. Binding of dTDP is stabilized by ionic interactions to the phosphate group and by a combination of ionic and hydrophobic interactions with the base. The active site, which is located in the center of the jelly roll, is formed by residues that are conserved in all known RmlC sequence homologues. The conservation of the active site residues suggests that the mechanism of action is also conserved and that the RmlC structure may be useful in guiding the design of antibacterial drugs.
Christendat
D
D
Division of Molecular and Structural Biology, Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada.
Saridakis
V
V
Dharamsi
A
A
Bochkarev
A
A
Pai
E F
EF
Arrowsmith
C H
CH
Edwards
A M
AM
D000595:Amino Acid Sequence; D001665:Binding Sites; D002238:Carbohydrate Epimerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D046911:Macromolecular Substances; D017014:Methanobacterium / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013942:Thymine Nucleotides / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins; D002237:Carbohydrate Dehydrogenases
D002238:Carbohydrate Epimerases; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D013942:Thymine Nucleotides; C027923:thymidine 5'-diphosphate; C020092:dTDP-4-ketorhamnose 3,5-epimerase; D001426:Bacterial Proteins; D002237:Carbohydrate Dehydrogenases