Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: gastroenteritis [ICD11:
1A40.0 
];
foodborne intoxication [ICD11:
1A1Y , ICD11:
XN4Q5 ];
infection due to Campylobacter jejuni [ICD11:
XN4Q5 ]
The structure was elucidated in this paperNCBI PubMed ID: 22787156Publication DOI: 10.1074/jbc.M112.390492Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: ccreuzen
uwo.ca
Institutions: Department of Microbiology and Immunology, Infectious Diseases Research Group, University of Western Ontario, London, Ontario N6A 5C1, Canada
The Campylobacter jejuni capsule is important for colonization and virulence in various infection models. In most strains, the capsule includes a modified heptose whose biological role and biosynthetic pathway are unknown. To decipher the biosynthesis pathway for the 6-deoxy-D-altro-heptose of strain 81-176, we previously showed that the 4,6-dehydratase WcbK and the reductase WcaG generated GDP-6-deoxy-D-manno-heptose, but the C3 epimerase necessary to form GDP-6-deoxy-D-altro-heptose was not identified. Herein, we characterized the putative C3/C5 epimerase Cjj1430 and C3/C5 epimerase/C4 reductase Cjj1427 from the capsular cluster. We demonstrate that GDP-6-deoxy-D-altro-heptose biosynthesis is more complex than anticipated and requires the sequential action of WcbK, Cjj1430, and Cjj1427. We show that Cjj1430 serves as C3 epimerase devoid of C5 epimerization activity and that Cjj1427 has no epimerization activity and only serves as a reductase to produce GDP-6-deoxy-D-altro-heptose. Cjj1430 and Cjj1427 are the only members of the C3/C5 epimerases and C3/C5 epimerase/C4 reductase families shown to have activity on a heptose substrate and to exhibit only one of their two to three potential activities, respectively. Furthermore, we show that although the reductase WcaG is not part of the main pathway, its presence and its product affect the outcome of the pathway in a complex regulatory loop involving Cjj1427. This work provides the grounds for the elucidation of similar pathways found in other C. jejuni strains and other pathogens. It provides new molecular tools for the synthesis of carbohydrate antigens useful for vaccination and for the screening of enzymatic inhibitors that may have antibacterial effects.
Campylobacter, Enzymes, carbohydrate biosynthesis, Capsule Synthesis, Epimerases, GDP-6-Deoxy-altro-heptose, Heptose Modification, Microbial Pathogenesis
Structure type: monomer
Location inside paper: p.29777, fig.1, P4: GDP-6-deoxy-4-keto-D-arabino-heptose
Trivial name: GDP-6-deoxy-4-keto-D-arabino-heptose
Compound class: nucleoside diphosphate sugar
Contained glycoepitopes: IEDB_141493,IEDB_149170,IEDB_190357
Methods: 13C NMR, 1H NMR, NMR-2D, DNA cloning, DNA techniques, MALDI-MS, MS/MS, biochemical methods, enzyme assay, CE, anion exchange chromatography
Enzymes that release or process the structure: Cjj1430 - GDP-manno-heptose C3 epimerase
Synthetic data: enzymatic
Comments, role: substrate for biosynthesis of GDP-6-deoxy-D-altro-heptose
Related record ID(s): 1075, 1979, 1980, 1982
NCBI Taxonomy refs (TaxIDs): 354242
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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