4YWA

Structural Insight into Divalent Galactoside Binding to Pseudomonas aeruginosa lectin LecA

Summary for 4YWA

• Entry DOI: 10.2210/pdb4ywa/pdb
• Descriptor: PA-I galactophilic lectin, CALCIUM ION, (2R,3R,4S,5R,6R,2'R,3'R,4'S,5'R,6'R)-2,2'-([(2R,3R,4S,5S,6S)-3,4-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2,5-diyl]bis{1H-1,2,3-triazole-1,4-diyl[(2S,3R,4S,5S,6S)-3,4-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2,5-diyl]-1H-1,2,3-triazole-1,4-diylmethanediyloxy})bis[6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol], ... (4 entities in total)
• Functional Keywords: galactosides, lectins, sugar binding protein
• Biological source: Pseudomonas aeruginosa
• Cellular location: Cytoplasm: Q05097
• Total number of polymer chains: 4
• Total formula weight: 53426.80

Authors

Visini, R.,Jin, X.,Michaud, G.,Bergmann, M.,Gillon, E.,Imberty, A.,Stocker, A.,Darbre, T.,Pieters, R.,Reymond, J.-L. (deposition date: 2015-03-20, release date: 2015-09-09, Last modification date: 2024-01-10)

Primary citation

Visini, R.,Jin, X.,Bergmann, M.,Michaud, G.,Pertici, F.,Fu, O.,Pukin, A.,Branson, T.R.,Thies-Weesie, D.M.,Kemmink, J.,Gillon, E.,Imberty, A.,Stocker, A.,Darbre, T.,Pieters, R.J.,Reymond, J.L.
Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA.
Acs Chem.Biol., 10:2455-2462, 2015

PubMed Abstract: Multivalent galactosides inhibiting Pseudomonas aeruginosa biofilms may help control this problematic pathogen. To understand the binding mode of tetravalent glycopeptide dendrimer GalAG2 [(Gal-β-OC6H4CO-Lys-Pro-Leu)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2] to its target lectin LecA, crystal structures of LecA complexes with divalent analog GalAG1 [(Gal-β-OC6H4CO-Lys-Pro-Leu)2Lys-Phe-Lys-Ile-NH2] and related glucose-triazole linked bis-galactosides 3u3 [Gal-β-O(CH2)n-(C2HN3)-4-Glc-β-(C2HN3)-[β-Glc-4-(N3HC2)]2-(CH2)n-O-β-Gal (n = 1)] and 5u3 (n = 3) were obtained, revealing a chelate bound 3u3, cross-linked 5u3, and monovalently bound GalAG1. Nevertheless, a chelate bound model better explaining their strong LecA binding and the absence of lectin aggregation was obtained by modeling for all three ligands. A model of the chelate bound GalAG2·LecA complex was also obtained rationalizing its unusually tight LecA binding (KD = 2.5 nM) and aggregation by lectin cross-linking. The very weak biofilm inhibition with divalent LecA inhibitors suggests that lectin aggregation is necessary for biofilm inhibition by GalAG2, pointing to multivalent glycoclusters as a unique opportunity to control P. aeruginosa biofilms.

PubMed: 26295304
DOI: 10.1021/acschembio.5b00302

Experimental method

X-RAY DIFFRACTION (1.192 Å)