Source:http://linkedlifedata.com/resource/pubmed/id/16963083
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2006-10-2
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pubmed:databankReference | |
pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Escherichia coli Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorine Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Glycosyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Heptoses,
http://linkedlifedata.com/resource/pubmed/chemical/lipooligosaccharide...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-2836
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
363
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
383-94
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pubmed:meshHeading |
pubmed-meshheading:16963083-Adenosine Diphosphate,
pubmed-meshheading:16963083-Amino Acid Sequence,
pubmed-meshheading:16963083-Binding Sites,
pubmed-meshheading:16963083-Escherichia coli,
pubmed-meshheading:16963083-Escherichia coli Proteins,
pubmed-meshheading:16963083-Fluorine Compounds,
pubmed-meshheading:16963083-Glycosyltransferases,
pubmed-meshheading:16963083-Heptoses,
pubmed-meshheading:16963083-Models, Molecular,
pubmed-meshheading:16963083-Molecular Sequence Data,
pubmed-meshheading:16963083-Molecular Structure,
pubmed-meshheading:16963083-Mutagenesis, Site-Directed,
pubmed-meshheading:16963083-Protein Folding,
pubmed-meshheading:16963083-Protein Structure, Tertiary,
pubmed-meshheading:16963083-Sequence Alignment
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pubmed:year |
2006
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pubmed:articleTitle |
Structure of the Escherichia coli heptosyltransferase WaaC: binary complexes with ADP and ADP-2-deoxy-2-fluoro heptose.
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pubmed:affiliation |
Laboratoire de Cristallographie et RMN Biologiques, UMR 8015 CNRS, Université Paris Descartes, Faculté de Pharmacie, 4, Avenue de l'Observatoire, F-75270 Paris cedex 06, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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