2gt1
|
E. coli heptosyltransferase WaaC.
OverviewOverview
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.
About this StructureAbout this Structure
2GT1 is a Single protein structure of sequence from Escherichia coli uti89. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the Escherichia coli heptosyltransferase WaaC: binary complexes with ADP and ADP-2-deoxy-2-fluoro heptose., Grizot S, Salem M, Vongsouthi V, Durand L, Moreau F, Dohi H, Vincent S, Escaich S, Ducruix A, J Mol Biol. 2006 Oct 20;363(2):383-94. Epub 2006 Jul 29. PMID:16963083
Page seeded by OCA on Wed Jan 23 15:26:48 2008