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PDBsum entry 1lts
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103 a.a.
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185 a.a.
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41 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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Refined structure of escherichia coli heat-Labile enterotoxin, A close relative of cholera toxin.
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Authors
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T.K.Sixma,
K.H.Kalk,
B.A.Van zanten,
Z.Dauter,
J.Kingma,
B.Witholt,
W.G.Hol.
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Ref.
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J Mol Biol, 1993,
230,
890-918.
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PubMed id
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Abstract
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Heat-labile enterotoxin (LT) from Escherichia coli is a bacterial protein toxin
with an AB5 multimer structure, in which the B pentamer has a membrane binding
function and the A subunit is needed for enzymatic activity. The LT crystal
structure has been solved using a combination of multiple isomorphous
replacement, fivefold averaging and molecular dynamics refinement. Phase
combination using all these sources of phase information was of crucial
importance for the chain tracing. The structure has now been refined to 1.95 A
resolution, resulting in a model containing 6035 protein atoms and 293 solvent
molecules with a crystallographic R-factor of 18.2% and good stereochemistry.
The B subunits are arranged as a highly stable pentamer with a donut shape. Each
subunit takes part in approximately 30 inter-subunit hydrogen bonds and six salt
bridges with its two neighbors, whilst burying a large surface area. The A
subunit has higher temperature factors and less well-defined secondary structure
than the B subunits. It interacts with the B pentamer mainly via the C-terminal
A2 fragment, which runs through the highly charged central pore of the B
subunits. The pore contains at least 66 water molecules, which fill the space
left by the A2 fragment. A detailed analysis of the contacts between A and B
subunits showed that most specific contacts occur at the entrance of the central
pore of the B pentamer, while the contacts within the pore are mainly
hydrophobic and water mediated, with the exception of two salt bridges. Only a
few contacts exist between the A1 fragment and the B pentamer, showing that the
A2 fragment functions as a "linker" of the A and B parts of the protein.
Interacting with the A subunit by the B subunits does not cause large deviations
from a common B subunit structure, and the 5-fold symmetry is well maintained. A
potential NAD(+)-binding site is located in an elongated crevice at the
interface of two small sheets in the A1 fragment. At the back of this crevice
the functionally important Arg7 makes a hydrogen bond connecting two strands,
which seems to be conserved across the ADP-ribosylating toxin family. The
putative catalytic residue (A1:Glu112) is located nearby, close to a very
hydrophobic region, which packs two loops together. This hydrophobic region may
be important for catalysis and membrane translocation.
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Secondary reference #1
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Title
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Lactose binding to heat-Labile enterotoxin revealed by x-Ray crystallography.
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Authors
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T.K.Sixma,
S.E.Pronk,
K.H.Kalk,
B.A.Van zanten,
A.M.Berghuis,
W.G.Hol.
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Ref.
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Nature, 1992,
355,
561-564.
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PubMed id
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Secondary reference #2
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Title
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Crystal structure of a cholera toxin-Related heat-Labile enterotoxin from e. Coli.
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Authors
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T.K.Sixma,
S.E.Pronk,
K.H.Kalk,
E.S.Wartna,
B.A.Van zanten,
B.Witholt,
W.G.Hol.
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Ref.
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Nature, 1991,
351,
371-377.
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PubMed id
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Secondary reference #3
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Title
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Native non-Isomorphism in the structure determination of heat labile enterotoxin (lt) from e. Coli
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Authors
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T.K.Sixma,
S.E.Pronk,
A.C.T.Van scheltinga,
A.Aguirre,
K.H.Kalk,
G.Vriend,
W.G.J.Hol.
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Ref.
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proceedings ccp4 study, 1991,
29,
133.
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