5A3O
Crystal structure of the LecB lectin from Pseudomonas aeruginosa in complex with Methyl 6-(cinnamido)-6-deoxy-alpha-D-mannopyranoside at 1.6 ansgtrom
Summary for 5A3O
| Entry DOI | 10.2210/pdb5a3o/pdb |
| Descriptor | FUCOSE-BINDING LECTIN PA-IIL, CALCIUM ION, methyl alpha-D-mannopyranoside, ... (6 entities in total) |
| Functional Keywords | glycoinhibitors, sugar binding protein |
| Biological source | PSEUDOMONAS AERUGINOSA |
| Total number of polymer chains | 4 |
| Total formula weight | 48766.69 |
| Authors | Sommer, R.,Hauck, D.,Varrot, A.,Audfray, A.,Imberty, A.,Titz, A. (deposition date: 2015-06-02, release date: 2015-07-22, Last modification date: 2024-01-10) |
| Primary citation | Sommer, R.,Hauck, D.,Varrot, A.,Wagner, S.,Audfray, A.,Prestel, A.,Moleer, H.M.,Imberty, A.,Titz, A. Cinnamide Derivatives of D-Mannose as Inhibitors of the Bacterial Virulence Factor Lecb from Pseudomonas Aeruginosa Chemistryopen, 4:756-, 2015 Cited by PubMed Abstract: Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen with high antibiotic resistance. Its lectin LecB was identified as a virulence factor and is relevant in bacterial adhesion and biofilm formation. Inhibition of LecB with carbohydrate-based ligands results in a decrease in toxicity and biofilm formation. We recently discovered two classes of potent drug-like glycomimetic inhibitors, that is, sulfonamides and cinnamides of d-mannose. Here, we describe the chemical synthesis and biochemical evaluation of more than 20 derivatives with increased potency compared to the unsubstituted cinnamide. The structure-activity relationship (SAR) obtained and the extended biophysical characterization allowed the experimental determination of the binding mode of these cinnamides with LecB. The established surface binding mode now allows future rational structure-based drug design. Importantly, all glycomimetics tested showed extended receptor residence times with half-lives in the 5-20 min range, a prerequisite for therapeutic application. Thus, the glycomimetics described here provide an excellent basis for future development of anti-infectives against this multidrug-resistant pathogen. PubMed: 27308201DOI: 10.1002/OPEN.201500162 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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