5ab1 | pdb_00005ab1

Complex of the FimH lectin with a beta-cyclodextrin C-linked alpha-D-mannoside in cocrystallized orthorhombic crystals at 2.00 A resolution

spinqualitylabelsall models 5ab1, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ab1 is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BCD, HP6, MAN, TA5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Publication Abstract from PubMed Recently, we extended the anti-adhesive concept showing that potent FimH antagonists can block the attachment of adherent-invasive E. coli (AIEC) colonizing the intestinal mucosa of patients with Crohn's disease (CD). In this work, we designed a small library of analogs of heptylmannoside (HM), a previously identified nanomolar FimH inhibitor, but displaying poor in vivo anti-adhesive effects. The anomeric oxygen atom was replaced by a sulfur or a methylene group to prevent hydrolysis by intestinal glycosidases, and chemical groups were attached at the end of the alkyl tail. Importantly, a lead compound was shown to reduce AIEC levels in the feces, colonic and ileal mucosa after oral administration in a transgenic mouse model of CD. The compound showed a preferable low bioavailability suggesting the possibility of setting up an innovative antiadhesive therapy for CD patients in which AIEC play a key role, with the water-soluble and non-cytotoxic FimH, antagonists developed here. The anti-adhesive strategy in Crohn's disease: orally active mannosides to decolonize pathogenic Escherichia coli from the gut.,Dorta DA, Sivignon A, Chalopin T, Dumych T, Roos G, Bilyy R, Deniaud D, Krammer EM, De Ruyck J, Lensink M, Bouckaert J, Barnich N, Gouin SG Chembiochem. 2016 Mar 4. doi: 10.1002/cbic.201600018. PMID:26946458 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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