5MAY
STRUCTURE OF THE LECB LECTIN FROM PSEUDOMONAS AERUGINOSA STRAIN PA14 IN COMPLEX WITH 2-Thiophenesulfonamide-N-(beta-L-fucopyranosyl methyl)
Summary for 5MAY
| Entry DOI | 10.2210/pdb5may/pdb |
| Related | 5a6q |
| Descriptor | Fucose-binding lectin PA-IIL, CALCIUM ION, beta-L-fucopyranose, ... (5 entities in total) |
| Functional Keywords | sugar binding protein, lectin, lecb, pseudomonas aeruginosa pa14, glycoinhibitors |
| Biological source | Pseudomonas aeruginosa (strain UCBPP-PA14) |
| Total number of polymer chains | 4 |
| Total formula weight | 48393.07 |
| Authors | Sommer, R.,Imberty, A.,Titz, A.,Varrot, A. (deposition date: 2016-11-07, release date: 2017-12-20, Last modification date: 2024-01-17) |
| Primary citation | Sommer, R.,Wagner, S.,Rox, K.,Varrot, A.,Hauck, D.,Wamhoff, E.C.,Schreiber, J.,Ryckmans, T.,Brunner, T.,Rademacher, C.,Hartmann, R.W.,Bronstrup, M.,Imberty, A.,Titz, A. Glycomimetic, Orally Bioavailable LecB Inhibitors Block Biofilm Formation of Pseudomonas aeruginosa. J. Am. Chem. Soc., 140:2537-2545, 2018 Cited by PubMed Abstract: The opportunistic Gram-negative bacterium Pseudomonas aeruginosa is a leading pathogen for infections of immuno-compromised patients and those suffering from cystic fibrosis. Its ability to switch from planktonic life to aggregates, forming the so-called biofilms, is a front-line mechanism of antimicrobial resistance. The bacterial carbohydrate-binding protein LecB is an integral component and necessary for biofilm formation. Here, we report a new class of drug-like low molecular weight inhibitors of the lectin LecB with nanomolar affinities and excellent receptor binding kinetics and thermodynamics. This class of glycomimetic inhibitors efficiently blocked biofilm formation of P. aeruginosa in vitro while the natural monovalent carbohydrate ligands failed. Furthermore, excellent selectivity and pharmacokinetic properties were achieved. Notably, two compounds showed good oral bioavailability, and high compound concentrations in plasma and urine were achieved in vivo. PubMed: 29272578DOI: 10.1021/jacs.7b11133 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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