Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA

Ricardo Visini; Xian Jin; Myriam Bergmann; Gaelle Michaud; Francesca Pertici; Ou Fu; Aliaksei Pukin; Thomas R. Branson; Dominique M E Thies-Weesie; Johan Kemmink; Emilie Gillon; Anne Imberty; Achim Stocker; Tamis Darbre; Roland J. Pieters; Jean Louis Reymond

doi:10.1021/acschembio.5b00302

Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA

Ricardo Visini, Xian Jin, Myriam Bergmann, Gaelle Michaud, Francesca Pertici, Ou Fu, Aliaksei Pukin, Thomas R. Branson, Dominique M E Thies-Weesie, Johan Kemmink, Emilie Gillon, Anne Imberty, Achim Stocker, Tamis Darbre, Roland J. Pieters, Jean Louis Reymond^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 (K_D = 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.

Original language	English
Pages (from-to)	2455-2462
Number of pages	8
Journal	ACS Chemical Biology
Volume	10
Issue number	11
DOIs	https://doi.org/10.1021/acschembio.5b00302
Publication status	Published - 20 Nov 2015

Access to Document

10.1021/acschembio.5b00302

acschembio.5b00302Final published version, 7.11 MBLicence: Taverne

Cite this

Visini, R., Jin, X., Bergmann, M., Michaud, G., Pertici, F., Fu, O., Pukin, A., Branson, T. R., Thies-Weesie, D. M. E., Kemmink, J., Gillon, E., Imberty, A., Stocker, A., Darbre, T., Pieters, R. J., & Reymond, J. L. (2015). Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA. ACS Chemical Biology, 10(11), 2455-2462. https://doi.org/10.1021/acschembio.5b00302

@article{c1245f910d884fbf91941bd0d7f0b8eb,

title = "Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA",

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.",

author = "Ricardo Visini and Xian Jin and Myriam Bergmann and Gaelle Michaud and Francesca Pertici and Ou Fu and Aliaksei Pukin and Branson, {Thomas R.} and Thies-Weesie, {Dominique M E} and Johan Kemmink and Emilie Gillon and Anne Imberty and Achim Stocker and Tamis Darbre and Pieters, {Roland J.} and Reymond, {Jean Louis}",

year = "2015",

month = nov,

day = "20",

doi = "10.1021/acschembio.5b00302",

language = "English",

volume = "10",

pages = "2455--2462",

journal = "ACS Chemical Biology",

issn = "1554-8929",

publisher = "American Chemical Society",

number = "11",

}

Visini, R, Jin, X, Bergmann, M, Michaud, G, Pertici, F, Fu, O, Pukin, A, Branson, TR, Thies-Weesie, DME, Kemmink, J, Gillon, E, Imberty, A, Stocker, A, Darbre, T, Pieters, RJ & Reymond, JL 2015, 'Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA', ACS Chemical Biology, vol. 10, no. 11, pp. 2455-2462. https://doi.org/10.1021/acschembio.5b00302

TY - JOUR

T1 - Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA

AU - Visini, Ricardo

AU - Jin, Xian

AU - Bergmann, Myriam

AU - Michaud, Gaelle

AU - Pertici, Francesca

AU - Fu, Ou

AU - Pukin, Aliaksei

AU - Branson, Thomas R.

AU - Thies-Weesie, Dominique M E

AU - Kemmink, Johan

AU - Gillon, Emilie

AU - Imberty, Anne

AU - Stocker, Achim

AU - Darbre, Tamis

AU - Pieters, Roland J.

AU - Reymond, Jean Louis

PY - 2015/11/20

Y1 - 2015/11/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947937385&partnerID=8YFLogxK

U2 - 10.1021/acschembio.5b00302

DO - 10.1021/acschembio.5b00302

M3 - Article

C2 - 26295304

AN - SCOPUS:84947937385

SN - 1554-8929

VL - 10

SP - 2455

EP - 2462

JO - ACS Chemical Biology

JF - ACS Chemical Biology

IS - 11

ER -

Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA

Abstract

Access to Document

Fingerprint

Cite this