1ORR

Crystal Structure of CDP-Tyvelose 2-Epimerase complexed with NAD and CDP

Summary for 1ORR

• Entry DOI: 10.2210/pdb1orr/pdb
• Descriptor: CDP-tyvelose-2-epimerase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, CYTIDINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: rossmann fold, short-chain dehydrogenase/reductase, isomerase
• Biological source: Salmonella typhi
• Total number of polymer chains: 4
• Total formula weight: 160818.76

Authors

Koropatkin, N.M.,Liu, H.,Holden, H.M. (deposition date: 2003-03-14, release date: 2003-08-26, Last modification date: 2024-02-14)

Primary citation

Koropatkin, N.M.,Liu, H.W.,Holden, H.M.
High Resolution X-ray Structure of Tyvelose Epimerase from Salmonella typhi
J.Biol.Chem., 278:20874-20881, 2003

PubMed Abstract: Tyvelose epimerase catalyzes the last step in the biosynthesis of tyvelose by converting CDP-d-paratose to CDP-d-tyvelose. This unusual 3,6-dideoxyhexose occurs in the O-antigens of some types of Gram-negative bacteria. Here we describe the cloning, protein purification, and high-resolution x-ray crystallographic analysis of tyvelose epimerase from Salmonella typhi complexed with CDP. The enzyme from S. typhi is a homotetramer with each subunit containing 339 amino acid residues and a tightly bound NAD+ cofactor. The quaternary structure of the enzyme displays 222 symmetry and can be aptly described as a dimer of dimers. Each subunit folds into two distinct lobes: the N-terminal motif responsible for NAD+ binding and the C-terminal region that harbors the binding site for CDP. The analysis described here demonstrates that tyvelose epimerase belongs to the short-chain dehydrogenase/reductase superfamily of enzymes. Indeed, its active site is reminiscent to that observed for UDP-galactose 4-epimerase, an enzyme that plays a key role in galactose metabolism. Unlike UDP-galactose 4-epimerase where the conversion of configuration occurs about C-4 of the UDP-glucose or UDP-galactose substrates, in the reaction catalyzed by tyvelose epimerase, the inversion of stereochemistry occurs at C-2. On the basis of the observed binding mode for CDP, it is possible to predict the manner in which the substrate, CDP-paratose, and the product, CDP-tyvelose, might be accommodated within the active site of tyvelose epimerase.

PubMed: 12642575
DOI: 10.1074/jbc.M301948200

Experimental method

X-RAY DIFFRACTION (1.5 Å)