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PDBsum entry 1w8h
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Sugar binding protein
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PDB id
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1w8h
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References listed in PDB file
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Key reference
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Title
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Structural basis for the interaction between human milk oligosaccharides and the bacterial lectin pa-Iil of pseudomonas aeruginosa.
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Authors
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S.Perret,
C.Sabin,
C.Dumon,
M.Pokorná,
C.Gautier,
O.Galanina,
S.Ilia,
N.Bovin,
M.Nicaise,
M.Desmadril,
N.Gilboa-Garber,
M.Wimmerová,
E.P.Mitchell,
A.Imberty.
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Ref.
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Biochem J, 2005,
389,
325-332.
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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One of the mechanisms contributing to the protection by breast-feeding of the
newborn against enteric diseases is related to the ability of human milk
oligosaccharides to prevent the attachment of pathogenic bacteria to the
duodenual epithelium. Indeed, a variety of fucosylated oligosaccharides,
specific to human milk, form part of the innate immune system. In the present
study, we demonstrate the specific blocking of PA-IIL, a fucose-binding lectin
of the human pathogen Pseudomonas aeruginosa, by milk oligosaccharides. Two
fucosylated epitopes, Lewis a and 3-fucosyl-lactose (Lewis x glucose analogue)
bind to the lectin with dissociation constants of 2.2x10(-7) M and 3.6x10(-7) M
respectively. Thermodynamic studies indicate that these interactions are
dominated by enthalpy. The entropy contribution is slightly favourable when
binding to fucose and to the highest-affinity ligand, Lewis a. The
high-resolution X-ray structures of two complexes of PA-IIL with milk
oligosaccharides allow the precise determination of the conformation of a
trisaccharide and a pentasaccharide. The different types of interaction between
the oligosaccharides and the protein involve not only hydrogen bonding, but also
calcium- and water-bridged contacts, allowing a rationalization of the
thermodynamic data. This study provides important structural information about
compounds that could be of general application in new therapeutic strategies
against bacterial infections.
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Secondary reference #1
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Title
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Structural basis for oligosaccharide-Mediated adhesion of pseudomonas aeruginosa in the lungs of cystic fibrosis patients.
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Authors
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E.Mitchell,
C.Houles,
D.Sudakevitz,
M.Wimmerova,
C.Gautier,
S.Pérez,
A.M.Wu,
N.Gilboa-Garber,
A.Imberty.
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Ref.
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Nat Struct Biol, 2002,
9,
918-921.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. Structure of the PA-IIL -fucose complex. Stick
representation of fucose and calcium ions as space-filling
models. a, Monomer of PA-IIL with numbering of  -strands
according to the greek-key motif (strands 1 -5). b, Dimer with
chain A in blue and chain B in green. c, Two perpendicular views
of the tetramer consisting of the asymmetric unit.
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Figure 2.
Figure 2. Interactions of PA-IIL with calcium ions and fucose.
a, Stick representation of the amino acids involved in binding.
Ca^2+ coordination bonds are shown as solid orange lines;
hydrogen bonds, as dashed green lines. Color coding is red,
oxygen; blue, nitrogen; black, carbon; and pink, Ca^2+. b,
Electrostatic surface representation (color coding from violet
for negative to orange for positive) of the PA-IIL-binding site
with Ca^2+ (large pink spheres) and fucose (stick model). c,
Stereo view of the final 2F[o] - F[c] electron density map
around the fucose molecule bound to subunit A. The density is
contoured at 1.0  .
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The above figures are
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
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