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PDBsum entry 2vmh
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Sugar binding protein
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PDB id
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2vmh
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References listed in PDB file
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Key reference
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Title
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Divergent modes of glycan recognition by a new family of carbohydrate-Binding modules.
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Authors
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K.J.Gregg,
R.Finn,
D.W.Abbott,
A.B.Boraston.
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Ref.
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J Biol Chem, 2008,
283,
12604-12613.
[DOI no: ]
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PubMed id
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Abstract
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The genomes of myonecrotic Clostridium perfringens isolates contain genes
encoding a large and fascinating array of highly modular glycoside hydrolase
enzymes. Although the catalytic activities of many of these enzymes are somewhat
predictable based on their amino acid sequences, the functions of their abundant
ancillary modules are not and remain poorly studied. Here, we present the
structural and functional analysis of a new family of ancillary
carbohydrate-binding modules (CBMs), CBM51, which was previously annotated in
data bases as the novel putative CBM domain. The high resolution crystal
structures of two CBM51 members, GH95CBM51 and GH98CBM51, from a putative family
95 alpha-fucosidase and from a family 98 blood group A/B antigen-specific
endo-beta-galactosidase, respectively, showed them to have highly similar
beta-sandwich folds. However, GH95CBM51 was shown by glycan microarray
screening, isothermal titration calorimetry, and x-ray crystallography to bind
galactose residues, whereas the same analyses of GH98CBM51 revealed specificity
for the blood group A/B antigens through non-conserved interactions. Overall,
this work identifies a new family of CBMs with many members having apparent
specificity for eukaryotic glycans, in keeping with the glycan-rich environment
C. perfringens would experience in its host. However, a wider bioinformatic
analysis of this CBM family also indicated a large number of members in
non-pathogenic environmental bacteria, suggesting a role in the recognition of
environmental glycans.
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Figure 3.
FIGURE 3. Fold and calcium binding of CBM51. Shown are
color-ramped schematic representations of GH95CBM51 with
methyl-β-D-galactose (A) and GH98CBM51 with the B antigen
trisaccharide (B), both with bound calcium atoms shown as pink
spheres and ligands in stick representation. C shows a schematic
representation of CBM6-1 from Clostridium stercorarium (Protein
Data Bank code 1uy4) (34), with its bound calcium atom shown as
a pink sphere and its bound xylotetraose ligand shown in stick
representation. This structure is a representative β-sandwich
CBM showing the common calcium-binding site.
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Figure 5.
FIGURE 5. Comparison of GH95CBM51, GH98CBM51, and other
CBM51 members. A, overlay of the GH95CBM51 (yellow) and
GH98CBM51 (magenta) carbohydrate-binding sites. Relevant side
chains involved in binding and ligands are shown in stick
representation, and the metal atoms are shown as spheres. B,
phylogenetic analysis of CBM51. The inset shows the complete
analysis and indicates the subfamilies. Subfamilies CBM51a and
CBM51b (circled in the inset) are expanded with detailed
entries. The green star denotes the GH98CBM51 entry, and the
blue star denotes the GH95CBM51 entry. C, alignment of
subfamilies CBM51a (indicated by the green vertical line) and
CBM51b (indicated by the blue vertical line). The entry
numbering corresponds to that in B. GH98CBM51 and GH95CBM51 are
indicated by stars as in B. The secondary structures for
GH98CBM51 and GH95CBM51 are shown above and below the alignment,
respectively. Yellow arrows denote β-strands, and the red
cylinder represents an  -helix. Residues
involved in ligand binding by GH98CBM51 and GH95CBM51 are
indicated above and below the alignment, respectively, by
arrowheads.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
12604-12613)
copyright 2008.
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