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Neutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding

Gajdos, Lukas ; Blakeley, Matthew P. ; Haertlein, Michael ; Forsyth, V. Trevor LU ; Devos, Juliette M. and Imberty, Anne (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.

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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
2024-04-04 03:52:49
@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}},
}