PDBsum entry 1orr

Isomerase

PDB id: 1orr

Contents

Protein chains

338 a.a. *

Ligands

NAD ×4

CDP ×4

Waters ×1079

* Residue conservation analysis

PDB id:

1orr

Name:

Isomerase

Title:

Crystal structure of cdp-tyvelose 2-epimerase complexed with NAD and cdp

Structure:

Cdp-tyvelose-2-epimerase. Chain: a, b, c, d. Engineered: yes

Source:

Salmonella typhi. Organism_taxid: 601. Gene: rfbe or sty2298. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.50Å R-factor: 0.179 R-free: 0.229

Authors:

N.M.Koropatkin,H.Liu,H.M.Holden

Key ref:

N.M.Koropatkin et al. (2003). High resolution x-ray structure of tyvelose epimerase from Salmonella typhi. J Biol Chem, 278, 20874-20881. PubMed id: 12642575 DOI: 10.1074/jbc.M301948200

Date:

14-Mar-03 Release date: 26-Aug-03

Protein chains

P14169  (RFBE_SALTI) -  CDP-paratose 2-epimerase from Salmonella typhi

Seq: 338 a.a.

Struc: 338 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.5.1.3.10 - CDP-paratose 2-epimerase.
• Pathway: CDP-abequose, CDP-ascarylose, CDP-pararose and CDP-tyrelose Biosynthesis
• Reaction: CDP-alpha-D-paratose = CDP-3,6-dideoxy-alpha-D-mannose
• Cofactor: NAD(+)

NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M301948200

J Biol Chem 278:20874-20881 (2003)

PubMed id: 12642575

High resolution x-ray structure of tyvelose epimerase from Salmonella typhi.

N.M.Koropatkin, H.W.Liu, H.M.Holden.

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.

Selected figure(s)

Figure 2.
FIG. 2. Ribbon representation of tyvelose epimerase. The tetrameric structure of the enzyme is shown in a. The A/B and C/D pairs of dimers are similar to the dimers observed in both the human and bacterial forms of UDP-galactose 4-epimerase. Bound ligands are depicted in ball-and-stick representations. A stereo view of one subunit of the tetramer is shown in b. The molecular architecture of the subunit can be envisioned as two lobes, as indicated in blue and green. The active site is wedged between these two lobes.

Figure 3.
FIG. 3. Close-up view of the tyvelose epimerase active site. Those amino acid residues that are located within 3.2 Å of the NAD^+ and CDP ligands are shown. The ligands are highlighted in yellow bonds. Ordered water molecules are indicated by the red spheres. For the sake of clarity, Val-84 and Trp-208 were omitted from the figure.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 20874-20881) copyright 2003.

Figures were selected by an automated process.