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PDBsum entry 1w3a
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Toxin/sugar binding protein
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PDB id
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1w3a
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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 analysis of the laetiporus sulphureus hemolytic pore-Forming lectin in complex with sugars.
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Authors
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J.M.Mancheño,
H.Tateno,
I.J.Goldstein,
M.Martínez-Ripoll,
J.A.Hermoso.
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Ref.
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J Biol Chem, 2005,
280,
17251-17259.
[DOI no: ]
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PubMed id
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Abstract
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LSL is a lectin produced by the parasitic mushroom Laetiporus sulphureus, which
exhibits hemolytic and hemagglutinating activities. Here, we report the crystal
structure of LSL refined to 2.6-A resolution determined by the single
isomorphous replacement method with the anomalous scatter (SIRAS) signal of a
platinum derivative. The structure reveals that LSL is hexameric, which was also
shown by analytical ultracentrifugation. The monomeric protein (35 kDa) consists
of two distinct modules: an N-terminal lectin module and a pore-forming module.
The lectin module has a beta-trefoil scaffold that bears structural similarities
to those present in toxins known to interact with galactose-related
carbohydrates such as the hemagglutinin component (HA1) of the progenitor toxin
from Clostridium botulinum, abrin, and ricin. On the other hand, the C-terminal
pore-forming module (composed of domains 2 and 3) exhibits three-dimensional
structural resemblances with domains 3 and 4 of the beta-pore-forming toxin
aerolysin from the Gram-negative bacterium Aeromonas hydrophila, and domains 2
and 3 from the epsilon-toxin from Clostridium perfringens. This finding reveals
the existence of common structural elements within the aerolysin-like family of
toxins that could be directly involved in membrane-pore formation. The crystal
structures of the complexes of LSL with lactose and N-acetyllactosamine reveal
two dissacharide-binding sites per subunit and permits the identification of
critical residues involved in sugar binding.
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Figure 1.
FIG. 1. Three-dimensional structure and topology diagram of
LSL. A, ribbon model of monomeric LSL. The figure is colored
from the N to C terminus in a progression from blue to red via
green. Numbers 1-23 indicate the corresponding  -strands
and H1-H7 are the single-turn 3[10] helices. B, topology diagram
of LSL. -Strands and 3[10]
helices are represented by arrows and cylinders, respectively.
The starting and ending sequence numbers for each secondary
structural element are given. The lectin module is represented
in green and the pore-forming module in brown. A was prepared
with BOBSCRIPT (52) and RASTER3D (53).
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Figure 3.
FIG. 3. Lactose and N-acetyllactosamine binding to the
lectin module of LSL. A, structure of the Lac molecule bound to
the  -motif of LSL. B,
three-dimensional structure of LacNAc bound to the -motif
of LSL. The models show the F[o] - F[c] electron density maps
contoured at 2.5  around the Lac molecule
initially calculated without including the disaccharide. C,
LacNAc bound to the -motif. The F[o] - F[c]
electron density map contoured at 3 calculated without
including the disaccharide is shown in blue around the bound
carbohydrate. Broken lines indicate hydrogen bonds between sugar
and protein residues. Color coding of secondary structure
elements:  -motif, blue; -motif,
red, -motif, green. D,
molecular surface of the -trefoil scaffold, with
the LacNAc molecules (as stick models) bound to the - and
-sites. The surface is
colored according to the electrostatic potential, blue for
positive and red for negative. E, structure of Lac bound to one
binding site in ricin B-chain (Protein Data Bank code 2AAI [PDB]
; Ref. 40). A-C were prepared with MOLSCRIPT (54) and RASTER3D
(53); the molecular surface was built with the program GRASP
(55).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2005,
280,
17251-17259)
copyright 2005.
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