PDBsum entry: 2nzw

Transferase

PDB-id: 2nzw

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

349 a.a. *

Ligands

SO4 ×3

Waters ×1735

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

2nzw

Name:

Transferase

Title:

Crystal structure of alpha1,3-fucosyltransferase

Structure:

Alpha1,3-fucosyltransferase. Chain: a, b, c. Fragment: c-termincal truncated domain. Engineered: yes

Source:

Helicobacter pylori. Organism_taxid: 210. Strain: nctc 11639. Gene: af008596. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

UniProt:

Chains A, B, C: O30511 (O30511_HELPY)

Seq:

Struc:

Seq:

478 a.a.

Struc:

349 a.a.

Key:

PfamB domain

Secondary structure

Resolution:

1.90Å

R-factor:

0.191

R-free:

0.242

Authors:

H.Y.Sun,T.P.Ko

Key ref:

H.Y.Sun et al. (2007). Structure and mechanism of Helicobacter pylori fucosyltransferase. A basis for lipopolysaccharide variation and inhibitor design.. J Biol Chem, 282, 9973-9982. [PubMed id: 17251184] [DOI: 10.1074/jbc.M610285200]

Date:

27-Nov-06

Release date:

23-Jan-07

Related entries:

2nzx
the same protein complexed with gdp
2nzy
the same protein complexed with gdp-fucose

Quick_links

Procheck

Surface

Key reference

DOI no: 10.1074/jbc.M610285200

J Biol Chem 282:9973-9982 (2007)

PubMed id: 17251184

Structure and mechanism of Helicobacter pylori fucosyltransferase. A basis for lipopolysaccharide variation and inhibitor design.

H.Y.Sun, S.W.Lin, T.P.Ko, J.F.Pan, C.L.Liu, C.N.Lin, A.H.Wang, C.H.Lin.

ABSTRACT

Helicobacter pylori alpha1,3-fucosyltransferase (FucT) is involved in catalysis to produce the Lewis x trisaccharide, the major component of the bacteria's lipopolysaccharides, which has been suggested to mimic the surface sugars in gastric epithelium to escape host immune surveillance. We report here three x-ray crystal structures of FucT, including the FucT.GDP-fucose and FucT.GDP complexes. The protein structure is typical of the glycosyltransferase-B family despite little sequence homology. We identified a number of catalytically important residues, including Glu-95, which serves as the general base, and Glu-249, which stabilizes the developing oxonium ion during catalysis. The residues Arg-195, Tyr-246, Glu-249, and Lys-250 serve to interact with the donor substrate, GDP-fucose. Variations in the protein and ligand conformations, as well as a possible FucT dimer, were also observed. We propose a catalytic mechanism and a model of polysaccharide binding not only to explain the observed variations in H. pylori lipopolysaccharides, but also to facilitate the development of potent inhibitors.

Selected figure(s)

Figure 4.
FIGURE 4. FucT active site and proposed reaction mechanism. A, proposed catalytic mechanism of FucT where Glu-95 serves as a general base. The developing positive charge on fucose is stabilized in part by Glu-249. B, a close-up stereo view of the FucT catalytic region showing the predicted LacNAc model (pink), GDP-fucose (blue), and the related FucT residues (gray), which are drawn as stick models. For clarity, only GlcNAc is displayed. Hydrogen bonds are represented as yellow dotted lines.

Figure 6.
FIGURE 6. The putative FucT dimer. A, in the dimer, the two C termini have the same orientation. This is consistent with the parallel leucine-zipper coiled-coil as predicted for the full-length enzyme. B, the enzyme is turned 90°, viewed along the dyad axis and shown. The domains in each monomer are color-coded as green (N-terminal domain), orange (C-terminal domain), and red (C terminus). GDP-fucose is shown as a stick model.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 9973-9982) copyright 2007.

Figures were selected by an automated process.