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PDBsum entry 2wn5
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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 substrate recognition in the enzymatic component of ADP-Ribosyltransferase toxin cdta from clostridium difficile.
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Authors
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A.Sundriyal,
A.K.Roberts,
C.C.Shone,
K.R.Acharya.
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Ref.
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J Biol Chem, 2009,
284,
28713-28719.
[DOI no: ]
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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 have
been manually determined.
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Abstract
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ADP-ribosylation is one of the favored modes of cell intoxication employed by
several bacteria. Clostridium difficile is recognized to be an important
nosocomial pathogen associated with considerable morbidity and attributable
mortality. Along with its two well known toxins, Toxin A and Toxin B, it
produces an ADP-ribosylating toxin that targets monomeric actin of the target
cell. Like other Clostridial actin ADP-ribosylating toxins, this binary toxin,
known as C. difficile toxin (CDT), is composed of two subunits, CDTa and CDTb.
In this study, we present high resolution crystal structures of CDTa in its
native form (at pH 4.0, 8.5, and 9.0) and in complex with ADP-ribose donors, NAD
and NADPH (at pH 9.0). The crystal structures of the native protein show
"pronounced conformational flexibility" confined to the active site region of
the protein and "enhanced" disorder at low pH, whereas the complex structures
highlight significant differences in "ligand specificity" compared with the
enzymatic subunit of a close homologue, Clostridium perfringens iota toxin.
Specifically in CDTa, two of the suggested catalytically important residues
(Glu-385 and Glu-387) seem to play no role or a less important role in ligand
binding. These structural data provide the first detailed information on
protein-donor substrate complex stabilization in CDTa, which may have
implications in understanding CDT recognition.
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Figure 2.
Stereo view of ARTT loop in CDTa (native and NAD-bound form)
and Ia (NAD-bound form).Green, CDTa-8.5; yellow, CDTa-9.0; cyan,
CDTa-NAD; magenta, Ia-NAD. Residue numbering is according to
CDTa (present structure). The corresponding residues in Ia are
Tyr-375, Glu-378, and Glu-380.
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Figure 4.
A, orientation of ARTT loop in CDTa (native and NAD bound
form). B, orientation of loop 304, which shows differences
between CDTa-4 and other structures. Green, CDTa-8.5; yellow,
CDTa9.0; magenta, CDTa-4.0; cyan, CDTa-NAD.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
28713-28719)
copyright 2009.
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