5mts | pdb_00005mts

Complex of FimH lectin with a TazMan (thiazolylaminomannosides) family member known as potent anti-adhesive agent at 2.6 A resolution

spinqualitylabelsall models 5mts, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mts is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: NI, XKA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FIMH_ECOLI Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally positioned at intervals in the structure of the type 1 fimbriae. In order to integrate FimH in the fimbriae FimF and FimG are needed. Publication Abstract from PubMed Thiazolylaminomannosides (TazMan) are FimH antagonists with anti-adhesive potential against adherent-invasive Escherichia coli (AIEC) promoting gut inflammation in patients with Crohn's disease (CD). The lead TazMan is highly potent in vitro but shows limited in vivo efficiency probably due to low pH stability and water solubility. We recently developed a second generation of stable TazMan but the anti-adhesive effect was decreased compared to the first. Here, we report the co-crystal structure of the lead TazMan in FimH, revealing that the anomeric NH and the second thiazole moiety provide a positive H-bonding interaction with a trapped water molecule, and pi-stacking with Tyrosine 48 of FimH, respectively. Consequently, we have developed NeoTazMan homologated with a methylene group for low pH and mannosidase stability with a conserved NH group and bearing various heterocyclic aglycons. Microencapsulation of the lead NeoTazMan in a gamma-cyclodextrin dramatically improved the water solubility without disrupting the FimH affinity or the anti-adhesive effect against AIEC isolated from patients with CD. Physiochemical tuning of potent E. coli antiadhesives by microencapsulation and methylene homologation.,Alvarez Dorta D, Chalopin T, Sivignon A, De Ruyck J, Dumych T, Bilyy R, Deniaud D, Barnich N, Bouckaert J, Gouin SG ChemMedChem. 2017 Mar 3. doi: 10.1002/cmdc.201700061. PMID:28257558 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adhesin 3D structures

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