Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
The structure was elucidated in this paperNCBI PubMed ID: 16963083Journal NLM ID: 2985088RPublisher: Elsevier
Correspondence: arnaud.ducruix
univ-paris5.fr
Institutions: Laboratoire de Cristallographie et RMN Biologiques, UMR 8015 CNRS, Universite Paris Descartes, Faculte de Pharmacie, 4, Avenue de lObservatoire, F-75270 Paris cedex 06, France, Mutabilis, 102, route de Noisy, F-93230 Romainville France, FUNDP Faculte des Sciences, Laboratoire de Chimie Bio-Organique, Rue de Bruxelles, 61, B-5000 Namur - Belgium, Ecole Normale Superieure, Departement de Chimie, UMR 8642 du CNRS, 24 rue Lhomond 75005 Paris, France
Lipopolysaccharides constitute the outer leaflet of the outer membrane of Gram-negative bacteria and are therefore essential for cell growth and viability. The heptosyltransferase WaaC is a glycosyltransferase (GT) involved in the synthesis of the inner core region of LPS. It catalyzes the addition of the first l-glycero-d-manno-heptose (heptose) molecule to one 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) residue of the Kdo(2)-lipid A molecule. Heptose is an essential component of the LPS core domain; its absence results in a truncated lipopolysaccharide associated with the deep-rough phenotype causing a greater susceptibility to antibiotic and an attenuated virulence for pathogenic Gram-negative bacteria. Thus, WaaC represents a promising target in antibacterial drug design. Here, we report the structure of WaaC from the Escherichia coli pathogenic strain RS218 alone at 1.9 A resolution, and in complex with either ADP or the non-cleavable analog ADP-2-deoxy-2-fluoro-heptose of the sugar donor at 2.4 A resolution. WaaC adopts the GT-B fold in two domains, characteristic of one glycosyltransferase structural superfamily. The comparison of the three different structures shows that WaaC does not undergo a domain rotation, characteristic of the GT-B family, upon substrate binding, but allows the substrate analog and the reaction product to adopt remarkably distinct conformations inside the active site. In addition, both binary complexes offer a close view of the donor subsite and, together with results from site-directed mutagenesis studies, provide evidence for a model of the catalytic mechanism.
Lipopolysaccharide, heptose, crystal structure, glycosyltransferase
Structure type: monomer
Location inside paper: p.384,fig.1
Trivial name: component of core oligosaccharide
Contained glycoepitopes: IEDB_137353,IEDB_140947
Methods: biochemical methods
Enzymes that release or process the structure: Heptosyltransferase WaaC
3D data: 3D data
Related record ID(s): 940
NCBI Taxonomy refs (TaxIDs): 562Reference(s) to other database(s): GlycomeDB:
25190
Show glycosyltransferases
There is only one chemically distinct structure:
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