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PDBsum entry 2eal
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Sugar binding protein
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PDB id
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2eal
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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 human galectin-9 n-Terminal carbohydrate recognition domain reveals unexpected properties that differ from the mouse orthologue.
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Authors
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M.Nagae,
N.Nishi,
S.Nakamura-Tsuruta,
J.Hirabayashi,
S.Wakatsuki,
R.Kato.
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Ref.
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J Mol Biol, 2008,
375,
119-135.
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PubMed id
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Abstract
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Galectins are a family of beta-galactoside-binding lectins that contain a
conserved carbohydrate recognition domain (CRD). They exhibit high affinities
for small beta-galactosides as well as variable binding specificities for
complex glycoconjugates. Structural and biochemical analyses of the mechanism
governing specific carbohydrate recognition provide a useful template to
elucidate the function of these proteins. Here we report the crystal structures
of the human galectin-9 N-terminal CRD (NCRD) in the presence of lactose and
Forssman pentasaccharide. Mouse galectin-9 NCRD, the structure of which was
previously solved by our group, forms a non-canonical dimer in both the crystal
state and in solution. Human galectin-9 NCRD, however, exists as a monomer in
crystals, despite a high sequence identity to the mouse homologue. Comparative
frontal affinity chromatography analysis of the mouse and human galectin-9 NCRDs
revealed different carbohydrate binding specificities, with disparate affinities
for complex glycoconjugates. Human galectin-9 NCRD exhibited a high affinity for
Forssman pentasaccharide; the association constant for mouse galectin-9 NCRD was
100-fold less than that observed for the human protein. The combination of
structural data with mutational studies demonstrated that non-conserved amino
acid residues on the concave surface were important for determination of target
specificities. The human galectin-9 NCRD exhibited greater inhibition of cell
proliferation than the mouse NCRD. We discuss the biochemical and structural
differences between highly homologous proteins from different species.
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