Neutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding
(2022) In Nature Communications 13(1).- Abstract
The opportunistic pathogen Pseudomonas aeruginosa, a major cause of nosocomial infections, uses carbohydrate-binding proteins (lectins) as part of its binding to host cells. The fucose-binding lectin, LecB, displays a unique carbohydrate-binding site that incorporates two closely located calcium ions bridging between the ligand and protein, providing specificity and unusually high affinity. Here, we investigate the mechanisms involved in binding based on neutron crystallography studies of a fully deuterated LecB/fucose/calcium complex. The neutron structure, which includes the positions of all the hydrogen atoms, reveals that the high affinity of binding may be related to the occurrence of a low-barrier hydrogen bond induced by the... (More)
The opportunistic pathogen Pseudomonas aeruginosa, a major cause of nosocomial infections, uses carbohydrate-binding proteins (lectins) as part of its binding to host cells. The fucose-binding lectin, LecB, displays a unique carbohydrate-binding site that incorporates two closely located calcium ions bridging between the ligand and protein, providing specificity and unusually high affinity. Here, we investigate the mechanisms involved in binding based on neutron crystallography studies of a fully deuterated LecB/fucose/calcium complex. The neutron structure, which includes the positions of all the hydrogen atoms, reveals that the high affinity of binding may be related to the occurrence of a low-barrier hydrogen bond induced by the proximity of the two calcium ions, the presence of coordination rings between the sugar, calcium and LecB, and the dynamic behaviour of bridging water molecules at room temperature. These key structural details may assist in the design of anti-adhesive compounds to combat multi-resistance bacterial infections.
(Less)
- author
- Gajdos, Lukas ; Blakeley, Matthew P. ; Haertlein, Michael ; Forsyth, V. Trevor LU ; Devos, Juliette M. and Imberty, Anne
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 13
- issue
- 1
- article number
- 194
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85122786911
- pmid:35017516
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-021-27871-8
- language
- English
- LU publication?
- yes
- id
- d69aeb23-9dce-41c9-8f9e-c7357ae12ab2
- date added to LUP
- 2022-03-01 11:01:01
- date last changed
- 2024-06-13 11:09:31
@article{d69aeb23-9dce-41c9-8f9e-c7357ae12ab2,
abstract = {{<p>The opportunistic pathogen Pseudomonas aeruginosa, a major cause of nosocomial infections, uses carbohydrate-binding proteins (lectins) as part of its binding to host cells. The fucose-binding lectin, LecB, displays a unique carbohydrate-binding site that incorporates two closely located calcium ions bridging between the ligand and protein, providing specificity and unusually high affinity. Here, we investigate the mechanisms involved in binding based on neutron crystallography studies of a fully deuterated LecB/fucose/calcium complex. The neutron structure, which includes the positions of all the hydrogen atoms, reveals that the high affinity of binding may be related to the occurrence of a low-barrier hydrogen bond induced by the proximity of the two calcium ions, the presence of coordination rings between the sugar, calcium and LecB, and the dynamic behaviour of bridging water molecules at room temperature. These key structural details may assist in the design of anti-adhesive compounds to combat multi-resistance bacterial infections.</p>}},
author = {{Gajdos, Lukas and Blakeley, Matthew P. and Haertlein, Michael and Forsyth, V. Trevor and Devos, Juliette M. and Imberty, Anne}},
issn = {{2041-1723}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Neutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding}},
url = {{http://dx.doi.org/10.1038/s41467-021-27871-8}},
doi = {{10.1038/s41467-021-27871-8}},
volume = {{13}},
year = {{2022}},
}