Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
NCBI PubMed ID: 15196942Journal NLM ID: 0155157Publisher: Elsevier
Correspondence: rusnati
med.unibs.it
Institutions: Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, viale Europa 11, 25123 Brescia, Italy
The HIV-1 transactivating factor (Tat) acts as an extracellular cytokine on target cells, including endothelium. Here, we report about the Tat-antagonist capacity of chemically sulfated derivatives of the Escherichia coli K5 polysaccharide. O-sulfated K5 with high sulfation degree (K5-OS(H)) and N,O-sulfated K5 with high (K5-N,OS(H)) or low (K5-N,OS(L)) sulfation degree, but not unmodified K5, N-sulfated K5, and O-sulfated K5 with low sulfation degree, bind to Tat preventing its interaction with cell surface heparan sulfate proteoglycans, cell internalization, and consequent HIV-LTR-transactivation. Also, K5-OS(H) and K5-N,OS(H) prevent the interaction of Tat to the vascular endothelial growth factor receptor-2 on endothelial cell (EC) surface. Finally, K5-OS(H) inhibits [Formula: see text] integrin/Tat interaction and EC adhesion to immobilized Tat. Consequently, K5-OS(H) and K5-N,OS(H) inhibit the angiogenic activity of Tat in vivo. In conclusion, K5 derivatives with distinct sulfation patterns bind extracellular Tat and modulate its interaction with cell surface receptors and affect its biological activities. These findings provide the basis for the design of novel extracellular Tat antagonists with possible implications in anti-AIDS therapies.
Escherichia coli, antagonist, extracellular, adhesion, heparan sulfate, Hiv-1, polysaccharide derivatives, proteoglycan, sulfation
Structure type: polymer chemical repeating unit
Location inside paper: text
Trivial name: K5 polysaccharide, K-antigen, N-acetyl heparosan, heparosan (N-acetylheparosan), heparosan, heparosan (glycosaminoglycan GAG), K5 CPS, heparosan (K5-antigen), N-acetylheparosan
Compound class: CPS, EPS, K-antigen, polysaccharide
Contained glycoepitopes: IEDB_115136,IEDB_137340,IEDB_140630,IEDB_141807,IEDB_151531,IEDB_153764,IEDB_423153
Methods: sulfation
Biological activity: binding to HIV-1 Tat protein antagonists
Comments, role: CPS has the same structure as a heparin precursor N-acetylheparosan
NCBI Taxonomy refs (TaxIDs): 562Reference(s) to other database(s): GTC:G26089XS, GlycomeDB:
656
Show glycosyltransferases
There is only one chemically distinct structure:
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