Taxonomic group: bacteria / Chlamydiae
(Phylum: Chlamydiae)
Host organism: Homo sapiens
Associated disease: trachoma [ICD11:
1C23 
, ICD11:
XN4Q4 ];
salpingitis [ICD11:
GA07 ];
pelvic inflammatory disease [ICD11:
GA05 , Sex: female];
infection due to Chlamydia trachomatis [ICD11:
XN4Q4 ]
NCBI PubMed ID: 21628561Journal NLM ID: 7505876Publisher: National Academy of Sciences
Correspondence: raetz
biochem.duke.edu
Institutions: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are the main lipid components of bacterial outer membranes and are essential for cell viability in most Gram-negative bacteria. Here we show that small molecule inhibitors of LpxC [UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase], the enzyme that catalyzes the first committed step in the biosynthesis of lipid A, block the synthesis of LOS in the obligate intracellular bacterial pathogen Chlamydia trachomatis. In the absence of LOS, Chlamydia remains viable and establishes a pathogenic vacuole ('inclusion') that supports robust bacterial replication. However, bacteria grown under these conditions were no longer infectious. In the presence of LpxC inhibitors, replicative reticulate bodies accumulated in enlarged inclusions but failed to express selected late-stage proteins and transition to elementary bodies, a Chlamydia developmental form that is required for invasion of mammalian cells. These findings suggest the presence of an outer membrane quality control system that regulates Chlamydia developmental transition to infectious elementary bodies and highlights the potential application of LpxC inhibitors as unique class of antichlamydial agents.
Lipooligosaccharide, lipid A, Chlamydia trachomatis, outer membrane
Structure type: oligomer
Location inside paper: p.10285, fig.1
Trivial name: genus-specific epitope
Compound class: core oligosaccharide
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_135515,IEDB_141807,IEDB_150760,IEDB_150908,IEDB_151531,IEDB_176772,IEDB_534865
Methods: genetic methods
Biosynthesis and genetic data: genetic data,biochemical data
NCBI Taxonomy refs (TaxIDs): 813
Show glycosyltransferases
There is only one chemically distinct structure:
Taxonomic group: bacteria / Chlamydiae
(Phylum: Chlamydiae)
Associated disease: trachoma [ICD11:
1C23 , ICD11:
XN4Q4 ];
infection due to Chlamydia trachomatis [ICD11:
XN4Q4 ];
infection due to Chlamydia [ICD11:
XN27H ]
NCBI PubMed ID: 24682362Publication DOI: 10.1074/jbc.M113.528224Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: sml
fz-borstel.de; svevans
uvic.ca
Institutions: From the Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8P 3P6, Canada, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 22, Borstel D-23845, Germany
The structure of the antigen-binding fragment of mAb S25-26 determined to 1.95 A resolution in complex with the Chlamydiaceae family-specific trisaccharide antigen Kdo(2→8)-Kdo(2→4)Kdo (Kdo=3-deoxy-α-D-manno-oct-2-ulopyranosonic acid) displays a germline-coded paratope that differs significantly from previously characterized Chlamydiaceae-specific mAbs, despite being raised against the identical immunogen. Unlike the terminal Kdo recognition pocket that promotes cross-reactivity in S25-2-type antibodies, S25-26 and the closely related S25-23 utilize a groove composed of germline residues to recognize the entire trisaccharide antigen and so confer strict specificity. Interest in S25-23 was sparked by its rare high muM affinity and strict specificity for the family-specific trisaccharide antigen; however, only the related antibody S25-26 proved amenable to crystallization. The structures of three unliganded forms of S25-26 have a labile complementary determining region H3 adjacent to significant glycosylation of the variable heavy chain on asparagine 85 in Framework Region 3. Analysis of the glycan reveals a heterogeneous mixture with a common root structure that contains an unusually high number of terminal αGal-Gal moieties. One of the few reported structures of glycosylated mAbs containing these epitopes is the therapeutic antibody Cetuximab; however, unlike Cetuximab, one of the unliganded structures in S25-26 shows significant order in the glycan with appropriate electron density for nine residues. The elucidation of the three dimensional structure of an αGal containing N-linked glycan on a mAb variable heavy chain has potential clinical interest, as they have been implicated in allergic response in patients receiving therapeutic antibodies.
antibodies, epitopes, MAb, Chlamydiaceae, N-linked glycan, lipopolysaccharide antigen
Structure type: oligomer
Location inside paper: abstract, p.16645
Trivial name: cross-reactive epitope
Compound class: core oligosaccharide, LPS
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659
Methods: X-ray, ELISA, ESI-MS, genetic methods, HPLC, crystallization, ITC
Comments, role: commerical synthetic trisaccharide. One of origins: Chlamydia sp. without species and strain assignment.
3D data: 3D data
Related record ID(s): 30243, 30244, 30245
NCBI Taxonomy refs (TaxIDs): 813,
810Reference(s) to other database(s): GlycomeDB:
5771
Show glycosyltransferases
There is only one chemically distinct structure:
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