PDBsum entry 4mo2

Isomerase

PDB id: 4mo2

Contents

Protein chains

365 a.a.

Ligands

SO4 ×2

FDA

GOL ×2

NH4 ×2

FAD

Waters ×777

PDB id:

4mo2

Name:

Isomerase

Title:

Crystal structure of udp-n-acetylgalactopyranose mutase from campylobacter jejuni

Structure:

Udp-galactopyranose mutase. Chain: b, a. Engineered: yes

Source:

Campylobacter jejuni subsp. Jejuni. Organism_taxid: 192222. Strain: 11168. Gene: cj1439c, glf. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.173 R-free: 0.212

Authors:

S.A.Dalrymple,C.Protsko,M.B.Poulin,T.L.Lowary,D.A.R.Sanders

Key ref:

M.B.Poulin et al. (2014). Specificity of a UDP-GalNAc pyranose-furanose mutase: a potential therapeutic target for Campylobacter jejuni infections. Chembiochem, 15, 47-56. PubMed id: 24302429 DOI: 10.1002/cbic.201300653

Date:

11-Sep-13 Release date: 01-Jan-14

Protein chains

Q0P8H5  (Q0P8H5_CAMJE) -  UDP-galactopyranose mutase from Campylobacter jejuni subsp. jejuni serotype O:2 (strain ATCC 700819 / NCTC 11168)

Seq: 368 a.a.

Struc: 365 a.a.

Enzyme reactions

• Enzyme class: E.C.5.4.99.9 - UDP-galactopyranose mutase.
• Pathway: UDP-glucose, UDP-galactose and UDP-glucuronate Biosynthesis
• Reaction: UDP-alpha-D-galactose = UDP-alpha-D-galactofuranose

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

Added reference

DOI no: 10.1002/cbic.201300653

Chembiochem 15:47-56 (2014)

PubMed id: 24302429

Specificity of a UDP-GalNAc pyranose-furanose mutase: a potential therapeutic target for Campylobacter jejuni infections.

M.B.Poulin, Y.Shi, C.Protsko, S.A.Dalrymple, D.A.Sanders, B.M.Pinto, T.L.Lowary.

ABSTRACT

Pyranose-furanose mutases are essential enzymes in the life cycle of a number of microorganisms, but are absent in mammalian systems, and hence represent novel targets for drug development. To date, all such mutases show preferential recognition of a single substrate (e.g., UDP-Gal). We report here the detailed structural characterization of the first bifunctional pyranose-furanose mutase, which recognizes both UDP-Gal and UDP-GalNAc. The enzyme under investigation (cjUNGM) is involved in the biosynthesis of capsular polysaccharides (CPSs) in Campylobacter jejuni 11168. These CPSs are known virulence factors that are required for adhesion and invasion of human epithelial cells. Using a combination of UV/visible spectroscopy, X-ray crystallography, saturation transfer difference NMR spectroscopy, molecular dynamics and CORCEMA-ST calculations, we have characterized the binding of the enzyme to both UDP-Galp and UDP-GalpNAc, and compared these interactions with those of a homologous monofunctional mutase enzyme from E. coli (ecUGM). These studies reveal that two arginines in cjUNGM, Arg59 and Arg168, play critical roles in the catalytic mechanism of the enzyme and in controlling its specificity to ultimately lead to a GalfNAc-containing CPS. In ecUGM, these arginines are replaced with histidine and lysine, respectively, and this results in an enzyme that is selective for UDP-Gal. We propose that these changes in amino acids allow C. jejuni 11168 to produce suitable quantities of the sugar nucleotide substrate required for the assembly of a CPS containing GalfNAc, which is essential for viability.