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PDBsum entry 2g7c
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Contents |
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* Residue conservation analysis
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PDB id:
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Toxin
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Title:
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Clostridium difficile toxin a fragment bound to agal(1,3)bgal(1,4) bglcnac
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Structure:
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Toxin a. Chain: a, b. Fragment: tcda fragment 2. Engineered: yes
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Source:
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Clostridium difficile. Organism_taxid: 1496. Strain: 48489. Gene: toxa, tcda. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.00Å
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R-factor:
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0.195
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R-free:
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0.236
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Authors:
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A.Greco,J.G.S.Ho,S.J.Lin,M.M.Palcic,M.Rupnik,K.K.S.Ng
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Key ref:
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A.Greco
et al.
(2006).
Carbohydrate recognition by Clostridium difficile toxin A.
Nat Struct Mol Biol,
13,
460-461.
PubMed id:
DOI:
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Date:
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28-Feb-06
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Release date:
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18-Apr-06
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PROCHECK
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Headers
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References
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P16154
(TCDA_CLODI) -
Toxin A from Clostridioides difficile
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Seq:
Struc:
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2710 a.a.
245 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 14 residue positions (black
crosses)
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Enzyme class 2:
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E.C.2.4.1.-
- ?????
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Enzyme class 3:
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E.C.3.4.22.-
- ?????
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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DOI no:
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Nat Struct Mol Biol
13:460-461
(2006)
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PubMed id:
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Carbohydrate recognition by Clostridium difficile toxin A.
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A.Greco,
J.G.Ho,
S.J.Lin,
M.M.Palcic,
M.Rupnik,
K.K.Ng.
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ABSTRACT
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Clostridium difficile TcdA is a large toxin that binds carbohydrates on
intestinal epithelial cells. A 2-A resolution cocrystal structure reveals two
molecules of alpha-Gal-(1,3)-beta-Gal-(1,4)-beta-GlcNAcO(CH(2))(8)CO(2)CH(3)
binding in an extended conformation to TcdA. Residues forming key contacts with
the trisaccharides are conserved in all seven putative binding sites in TcdA,
suggesting a mode of multivalent binding that may be exploited for the rational
design of novel therapeutics.
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Selected figure(s)
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Figure 1.
Figure 1. Structure of TcdA-f2. (a) Ribbon structure and
schematic with SRs (dark blue), SR3 and SR6 (cyan), and LRs
(green) highlighted. (b) Ribbon representation of TcdA-f2 and
bound trisaccharides, viewed from the N terminus. The
reducing-end  -GlcNAc
is colored yellow.
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Figure 2.
Figure 2. TcdA-f2 bound to CD-grease at BS1A. Hydrogen bonds
are drawn as dashed lines.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
460-461)
copyright 2006.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Agostino,
M.S.Sandrin,
P.E.Thompson,
E.Yuriev,
and
P.A.Ramsland
(2010).
Identification of preferred carbohydrate binding modes in xenoreactive antibodies by combining conformational filters and binding site maps.
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Glycobiology,
20,
724-735.
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R.N.Pruitt,
M.G.Chambers,
K.K.Ng,
M.D.Ohi,
and
D.B.Lacy
(2010).
Structural organization of the functional domains of Clostridium difficile toxins A and B.
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Proc Natl Acad Sci U S A,
107,
13467-13472.
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M.R.Popoff,
and
P.Bouvet
(2009).
Clostridial toxins.
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Future Microbiol,
4,
1021-1064.
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R.N.Pruitt,
B.Chagot,
M.Cover,
W.J.Chazin,
B.Spiller,
and
D.B.Lacy
(2009).
Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A.
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J Biol Chem,
284,
21934-21940.
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PDB code:
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C.Y.Yeh,
C.N.Lin,
C.F.Chang,
C.H.Lin,
H.T.Lien,
J.Y.Chen,
and
J.S.Chia
(2008).
C-terminal repeats of Clostridium difficile toxin A induce production of chemokine and adhesion molecules in endothelial cells and promote migration of leukocytes.
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Infect Immun,
76,
1170-1178.
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D.A.Bobak
(2008).
The Molecular Pathogenesis of Clostridium difficile-associated Disease.
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Curr Infect Dis Rep,
10,
111-115.
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H.Genth,
S.C.Dreger,
J.Huelsenbeck,
and
I.Just
(2008).
Clostridium difficile toxins: more than mere inhibitors of Rho proteins.
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Int J Biochem Cell Biol,
40,
592-597.
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M.S.Salnikova,
S.B.Joshi,
J.H.Rytting,
M.Warny,
and
C.R.Middaugh
(2008).
Preformulation studies of Clostridium difficile toxoids A and B.
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J Pharm Sci,
97,
4194-4207.
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M.S.Salnikova,
S.B.Joshi,
J.H.Rytting,
M.Warny,
and
C.R.Middaugh
(2008).
Physical characterization of clostridium difficile toxins and toxoids: effect of the formaldehyde crosslinking on thermal stability.
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J Pharm Sci,
97,
3735-3752.
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T.Giesemann,
M.Egerer,
T.Jank,
and
K.Aktories
(2008).
Processing of Clostridium difficile toxins.
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J Med Microbiol,
57,
690-696.
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T.Jank,
and
K.Aktories
(2008).
Structure and mode of action of clostridial glucosylating toxins: the ABCD model.
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Trends Microbiol,
16,
222-229.
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X.Na,
H.Kim,
M.P.Moyer,
C.Pothoulakis,
and
J.T.LaMont
(2008).
gp96 is a human colonocyte plasma membrane binding protein for Clostridium difficile toxin A.
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Infect Immun,
76,
2862-2871.
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M.Egerer,
T.Giesemann,
T.Jank,
K.J.Satchell,
and
K.Aktories
(2007).
Auto-catalytic cleavage of Clostridium difficile toxins A and B depends on cysteine protease activity.
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J Biol Chem,
282,
25314-25321.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
