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| [[Image:2gt1.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2gt1| PDB=2gt1 | SCENE= }} | | {{STRUCTURE_2gt1| PDB=2gt1 | SCENE= }} |
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| '''E. coli heptosyltransferase WaaC.'''
| | ===E. coli heptosyltransferase WaaC.=== |
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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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16963083}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16963083 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16963083}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Vongsouthi, V.]] | | [[Category: Vongsouthi, V.]] |
| [[Category: Gt-b fold]] | | [[Category: Gt-b fold]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:29:49 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:16:35 2008'' |