8AIJ

STRUCTURE OF THE LECB LECTIN FROM PSEUDOMONAS AERUGINOSA STRAIN PAO1 IN COMPLEX WITH N-(alpha-L-Fucopyranosyl)benzamide (6)

This is a non-PDB format compatible entry.

Summary for 8AIJ

• Entry DOI: 10.2210/pdb8aij/pdb
• Descriptor: Fucose-binding lectin PA-IIL, CALCIUM ION, N-(alpha-L-Fucopyranosyl)benzamide, ... (5 entities in total)
• Functional Keywords: p. aeruginosa lectin, lecb, inhibitor, sugar binding protein
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 4
• Total formula weight: 48576.84

Authors

Meiers, J.,Mala, P.,Varrot, A.,Siebs, E.,Imberty, A.,Titz, A. (deposition date: 2022-07-26, release date: 2022-11-02, Last modification date: 2024-01-31)

Primary citation

Mala, P.,Siebs, E.,Meiers, J.,Rox, K.,Varrot, A.,Imberty, A.,Titz, A.
Discovery of N -beta-l-Fucosyl Amides as High-Affinity Ligands for the Pseudomonas aeruginosa Lectin LecB.
J.Med.Chem., 65:14180-14200, 2022

PubMed Abstract: The Gram-negative pathogen causes severe infections mainly in immunocompromised or cystic fibrosis patients and is able to resist antimicrobial treatments. The extracellular lectin LecB plays a key role in bacterial adhesion to the host and biofilm formation. For the inhibition of LecB, we designed and synthesized a set of fucosyl amides, sulfonamides, and thiourea derivatives. Then, we analyzed their binding to LecB in competitive and direct binding assays. We identified β-fucosyl amides as unprecedented high-affinity ligands in the two-digit nanomolar range. X-ray crystallography of one α- and one β-anomer of -fucosyl amides in complex with LecB revealed the interactions responsible for the high affinity of the β-anomer at atomic level. Further, the molecules showed good stability in murine and human blood plasma and hepatic metabolism, providing a basis for future development into antibacterial drugs.

PubMed: 36256875
DOI: 10.1021/acs.jmedchem.2c01373

Experimental method

X-RAY DIFFRACTION (1.5 Å)