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2h1h

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{{STRUCTURE_2h1h| PDB=2h1h | SCENE= }}
{{STRUCTURE_2h1h| PDB=2h1h | SCENE= }}
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'''E. coli heptosyltransferase WaaC with ADP-2-deoxy-2-fluoro heptose'''
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===E. coli heptosyltransferase WaaC with ADP-2-deoxy-2-fluoro heptose===
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==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Absence of c-terminal alpha-helix]]
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Revision as of 04:08, 29 July 2008

Template:STRUCTURE 2h1h

E. coli heptosyltransferase WaaC with ADP-2-deoxy-2-fluoro heptose

Template:ABSTRACT PUBMED 16963083

About this Structure

2H1H is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

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

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