9HD4

LecB in complex with photoswitchable compound GTB

This is a non-PDB format compatible entry.

Summary for 9HD4

• Entry DOI: 10.2210/pdb9hd4/pdb
• Descriptor: Fucose-binding lectin PA-IIL, ~{N}-[[(2~{R},3~{S},4~{R},5~{S},6~{S})-6-methyl-3,4,5-tris(oxidanyl)oxan-2-yl]methyl]-4-[(~{Z})-phenyldiazenyl]benzenesulfonamide, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: lectin, cell adhesion, sugar binding protein, photoswitchable ligand
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 4
• Total formula weight: 48793.49

Authors

Parisini, E.,Bhattacharya, S. (deposition date: 2024-11-11, release date: 2025-11-19, Last modification date: 2026-01-28)

Primary citation

Bhattacharya, S.,Tempra, G.,Colleoni, A.,Matera, C.,Castagna, R.,Parisini, E.
Synthesis, photochemical and biological evaluation of novel photoswitchable glycomimetic ligands of Pseudomonas aeruginosa LecB.
Rsc Adv, 15:49796-49808, 2025

PubMed Abstract: Bacterial multidrug resistance (MDR) poses a major threat to global health. The continued use of antibiotics, combined with genetic variations and exposure to nosocomial infections, has led to the selection and spread of multidrug-resistant bacteria. In recent years, photopharmacology has emerged as a strategy to combat MDR by enabling precise, light-controlled spatiotemporal modulation of the biological activity of photo-switchable compounds. Among different microbial species, is a prominent bacterium involved in acute and chronic lung infections, posing a significant health concern, particularly among hospitalized and immunocompromised patients. The bacterium's capacity to form biofilms, a key factor in the development of MDR, is closely linked to the activity of the virulence factor LecB, a carbohydrate-binding protein with a well-documented role in biofilm formation. In this study, we report the design, synthesis and biological evaluation of two novel photoswitchable LecB modulators, photofucose-1 and photofucose-2. Isothermal Titration Calorimetry (ITC) analysis revealed that photofucose-2 binds LecB with high affinity, exhibiting a distinct difference in dissociation constants ( ) between its and isomers. Moreover, we determined the X-ray crystal structure of the LecB-photofucose-2 complex, offering insights into its binding mechanism. These findings lay the groundwork for the rational, structure-based design of novel light-responsive compounds targeting LecB and represent a potential new avenue in the development of innovative strategies to combat bacterial resistance.

PubMed: 41393209
DOI: 10.1039/d5ra06897e

Experimental method

X-RAY DIFFRACTION (1.491 Å)