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PDBsum entry 1xtc
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192 a.a.
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45 a.a.
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103 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The three-Dimensional crystal structure of cholera toxin.
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Authors
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R.G.Zhang,
D.L.Scott,
M.L.Westbrook,
S.Nance,
B.D.Spangler,
G.G.Shipley,
E.M.Westbrook.
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Ref.
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J Mol Biol, 1995,
251,
563-573.
[DOI no: ]
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PubMed id
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Abstract
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The clinical manifestations of cholera are largely attributable to the actions
of a secreted hexameric AB5 enterotoxin (choleragen). We have independently
solved and refined the three-dimensional structure of choleragen at 2.5 A
resolution. The structure of the crystalline toxin closely resembles that
described for the heat-labile enterotoxin from Escherichia coli (LT) with which
it shares 80% sequence homology. In both cases, the wedge-shaped A subunit is
loosely held high above the plane of the pentameric B subunits by the tethering
A2 chain. The most striking difference between the two toxins occurs at the
carboxyl terminus of the A2 chain. Whereas the last 14 residues of the A2 chain
of LT threading through the central pore of the B5 assembly form an extended
chain with a terminal loop, the A2 chain of choleragen remains a nearly
continuous alpha-helix throughout its length. The four carboxyl-terminal
residues of the A2 chain (KDEL sequence), disordered in the crystal structure of
LT, are clearly visible in choleragen's electron-density map. In the
accompanying article we describe the three-dimensional structure of the isolated
B pentamer of cholera toxin (choleragenoid). Comparison of the crystalline
coordinates of choleragen, choleragenoid, and LT provides a solid
three-dimensional foundation for further experimental investigation. These
structures, along with those of related toxins from Shigella dysenteria and
Bordetella pertussis, offer a first step towards the rational design of new
vaccines and anti-microbial agents.
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Figure 3.
Figure 3. Representative electron-density for cholera toxin. Stereo view of the 2Fo--Fc electron-density map at the junction
between the A subunit and the B pentamer. The long A2 a-helix (orange) can be seen as it begins its descent into the
central pore. Residues belonging to the A1 chain or to the B pentamer are indicated (Pro120 and Ala(4)75, respectively).
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Figure 9.
Figure 9. Cross-section through the central ``channel'' of choleragen. The A1 chain, A2 chain, and the B subunits are
colored cyan, gold, and lavender, respectively. Side-chains contributing to the A2/B interface are shaded according to
charge potential: green, non-polar; red, negatively charged; blue, positively charged. The Trp88 of opposed B subunits
are shown to assist with orientation. Yellow spheres represent well-resolved water molecules. TheA2/B interface is initially
quite non-polar but becomes quite polar deeper in the channel. The carboxyl terminus of the A2 chain presumably interacts
with the surface of the membrane during GM1 binding. The sequence of the terminal four residues (KDEL) is identical
to that shown to act as endoplasmic retention signal (Lewis & Pelham, 1990; Joseph et al., 1978, 1979).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1995,
251,
563-573)
copyright 1995.
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Secondary reference #1
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Title
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The 2.4 a crystal structure of cholera toxin b subunit pentamer: choleragenoid.
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Authors
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R.G.Zhang,
M.L.Westbrook,
E.M.Westbrook,
D.L.Scott,
Z.Otwinowski,
P.R.Maulik,
R.A.Reed,
G.G.Shipley.
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Ref.
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J Mol Biol, 1995,
251,
550-562.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. Overview of the crystalline choleragenoid. A, Stereo pair of the pentamer viewed from the ``side'' (along an
axis perpendicular to the 5-fold axis). Each subunit is colored differently with only the side-chains of Tyr12, Gln56, and
Trp88 shown (green). These residues surround the GM1-binding sites located adjacent to the ``ventral'' flange of
choleragenoid. The A subunit of the holotoxin lies on top of the ``dorsal'' surface. The disulfide bridges between residues
9 and 86 are colored magenta. The amino and carboxyl termini are shown as blue and red spheres, respectively. B, Stereo
pair of the pentamer viewed from the ``ventral'' surface (along an axis parallel to the 5-fold). Residues are indicated as
in A. The central pore of choleragen is occupied by the helical terminus of the A2 chain in the holotoxin (Zhang et al.,
1995).
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Figure 7.
Figure 7. The central pore of choleragenoid and choleragen. Cross-section through the central pore of (A) choleragenoid,
and (B) choleragen (Zhang et al., 1995) along the 5-fold axis. For clarity, only the side-chains of the central a-helices are
shown (magenta). Solvent molecules are indicates as yellow spheres. The carboxyl end of the A2 chain (gold) occupies
the central pore of choleragen. Part of the A1 chain (cyan) is also shown in B for orientation purposes. In the absence of
the A2 chain, the pore is a highly solvated channel. The location of the ganglioside-binding site is indicated by the
side-chain of Trp88 (green).
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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