2GT1

E. coli heptosyltransferase WaaC.

Summary for 2GT1

• Entry DOI: 10.2210/pdb2gt1/pdb
• Descriptor: Lipopolysaccharide heptosyltransferase-1 (2 entities in total)
• Functional Keywords: gt-b fold, transferase
• Biological source: Escherichia coli UTI89
• Total number of polymer chains: 2
• Total formula weight: 72549.03

Authors

Grizot, S.,Salem, M.,Vongsouthi, V.,Durand, L.,Moreau, F.,Dohi, H.,Vincent, S.,Escaich, S.,Ducruix, A. (deposition date: 2006-04-27, release date: 2007-05-01, Last modification date: 2024-02-14)

Primary citation

Grizot, S.,Salem, M.,Vongsouthi, V.,Durand, L.,Moreau, F.,Dohi, H.,Vincent, S.,Escaich, S.,Ducruix, A.
Structure of the Escherichia coli Heptosyltransferase WaaC: Binary Complexes with ADP AND ADP-2-deoxy-2-fluoro Heptose.
J.Mol.Biol., 363:383-394, 2006

PubMed Abstract: 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 Kdo2-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.

PubMed: 16963083
DOI: 10.1016/j.jmb.2006.07.057

Experimental method

X-RAY DIFFRACTION (1.9 Å)