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Contents |
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264 a.a.
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(+ 4 more)
69 a.a.
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* Residue conservation analysis
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PDB id:
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| Name: |
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Toxin
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Title:
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Shiga toxin
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Structure:
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Shiga toxin a subunit. Chain: a, l. Engineered: yes. Shiga toxin b subunit. Chain: b, c, d, e, f, g, h, i, j, k. Engineered: yes
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Source:
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Shigella dysenteriae. Organism_taxid: 622. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Hexamer (from
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Resolution:
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Authors:
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M.E.Fraser,M.M.Chernaia,Y.V.Kozlov,M.N.James
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Key ref:
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M.E.Fraser
et al.
(1994).
Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A resolution.
Nat Struct Biol,
1,
59-64.
PubMed id:
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Date:
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13-Dec-99
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Release date:
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30-Dec-99
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PROCHECK
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Headers
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References
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Enzyme class:
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Chains A, L:
E.C.3.2.2.22
- rRNA N-glycosylase.
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Reaction:
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Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.
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Nat Struct Biol
1:59-64
(1994)
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PubMed id:
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Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A resolution.
|
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M.E.Fraser,
M.M.Chernaia,
Y.V.Kozlov,
M.N.James.
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ABSTRACT
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Shigella dysenteriae is the pathogen responsible for the severe form of
dysentery in humans. It produces Shiga toxin, the prototype of a family of
closely related bacterial protein toxins. We have determined the structure of
the holotoxin, an AB5 hexamer, by X-ray crystallography. The five B subunits
form a pentameric ring, encircling a helix at the carboxy terminus of the A
subunit. The A subunit interacts with the B pentamer via this C-terminal helix
and a four-stranded mixed beta-sheet. The fold of the rest of the A subunit is
similar to that of the A chain of the plant toxin ricin; both are
N-glycosidases. However, the active site in the bacterial holotoxin is blocked
by a segment of polypeptide chain. These residues of the A subunit would be
released as part of the activation mechanism of the toxin.
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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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|
|
|
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B.Seantier,
M.Dezi,
F.Gubellini,
A.Berquand,
C.Godefroy,
P.Dosset,
D.Lévy,
and
P.E.Milhiet
(2011).
Transfer on hydrophobic substrates and AFM imaging of membrane proteins reconstituted in planar lipid bilayers.
|
| |
J Mol Recognit,
24,
461-466.
|
|
|
|
|
|
|
A.Panda,
I.Tatarov,
A.R.Melton-Celsa,
K.Kolappaswamy,
E.H.Kriel,
D.Petkov,
T.Coksaygan,
S.Livio,
C.G.McLeod,
J.P.Nataro,
A.D.O'Brien,
and
L.J.DeTolla
(2010).
Escherichia coli O157:H7 infection in Dutch belted and New Zealand white rabbits.
|
| |
Comp Med,
60,
31-37.
|
|
|
|
|
|
|
D.G.Conrady,
M.J.Flagler,
D.R.Friedmann,
B.D.Vander Wielen,
R.A.Kovall,
A.A.Weiss,
and
A.B.Herr
(2010).
Molecular basis of differential B-pentamer stability of Shiga toxins 1 and 2.
|
| |
PLoS One,
5,
e15153.
|
|
|
PDB code:
|
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|
|
|
|
|
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D.Leyva-Illades,
R.P.Cherla,
C.L.Galindo,
A.K.Chopra,
and
V.L.Tesh
(2010).
Global transcriptional response of macrophage-like THP-1 cells to Shiga toxin type 1.
|
| |
Infect Immun,
78,
2454-2465.
|
|
|
|
|
|
|
L.Johannes,
and
W.Römer
(2010).
Shiga toxins--from cell biology to biomedical applications.
|
| |
Nat Rev Microbiol,
8,
105-116.
|
|
|
|
|
|
|
M.C.Cheung,
L.Revers,
S.Perampalam,
X.Wei,
R.Kiarash,
D.E.Green,
A.Abdul-Wahid,
and
J.Gariépy
(2010).
An evolved ribosome-inactivating protein targets and kills human melanoma cells in vitro and in vivo.
|
| |
Mol Cancer,
9,
28.
|
|
|
|
|
|
|
M.S.Lee,
R.P.Cherla,
E.K.Lentz,
D.Leyva-Illades,
and
V.L.Tesh
(2010).
Signaling through C/EBP homologous protein and death receptor 5 and calpain activation differentially regulate THP-1 cell maturation-dependent apoptosis induced by Shiga toxin type 1.
|
| |
Infect Immun,
78,
3378-3391.
|
|
|
|
|
|
|
V.L.Tesh
(2010).
Induction of apoptosis by Shiga toxins.
|
| |
Future Microbiol,
5,
431-453.
|
|
|
|
|
|
|
B.Windschiegl,
A.Orth,
W.Römer,
L.Berland,
B.Stechmann,
P.Bassereau,
L.Johannes,
and
C.Steinem
(2009).
Lipid reorganization induced by Shiga toxin clustering on planar membranes.
|
| |
PLoS One,
4,
e6238.
|
|
|
|
|
|
|
M.J.Smith,
A.R.Melton-Celsa,
J.F.Sinclair,
H.M.Carvalho,
C.M.Robinson,
and
A.D.O'Brien
(2009).
Monoclonal antibody 11E10, which neutralizes shiga toxin type 2 (Stx2), recognizes three regions on the Stx2 A subunit, blocks the enzymatic action of the toxin in vitro, and alters the overall cellular distribution of the toxin.
|
| |
Infect Immun,
77,
2730-2740.
|
|
|
|
|
|
|
P.H.Too,
M.K.Ma,
A.N.Mak,
Y.T.Wong,
C.K.Tung,
G.Zhu,
S.W.Au,
K.B.Wong,
and
P.C.Shaw
(2009).
The C-terminal fragment of the ribosomal P protein complexed to trichosanthin reveals the interaction between the ribosome-inactivating protein and the ribosome.
|
| |
Nucleic Acids Res,
37,
602-610.
|
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PDB codes:
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|
|
J.E.Lee,
J.Reed,
M.S.Shields,
K.M.Spiegel,
L.D.Farrell,
and
P.P.Sheridan
(2007).
Phylogenetic analysis of Shiga toxin 1 and Shiga toxin 2 genes associated with disease outbreaks.
|
| |
BMC Microbiol,
7,
109.
|
|
|
|
|
|
|
L.J.Peek,
R.N.Brey,
and
C.R.Middaugh
(2007).
A rapid, three-step process for the preformulation of a recombinant ricin toxin A-chain vaccine.
|
| |
J Pharm Sci,
96,
44-60.
|
|
|
|
|
|
|
M.Nangaku,
H.Nishi,
and
T.Fujita
(2007).
Pathogenesis and prognosis of thrombotic microangiopathy.
|
| |
Clin Exp Nephrol,
11,
107-114.
|
|
|
|
|
|
|
W.Römer,
L.Berland,
V.Chambon,
K.Gaus,
B.Windschiegl,
D.Tenza,
M.R.Aly,
V.Fraisier,
J.C.Florent,
D.Perrais,
C.Lamaze,
G.Raposo,
C.Steinem,
P.Sens,
P.Bassereau,
and
L.Johannes
(2007).
Shiga toxin induces tubular membrane invaginations for its uptake into cells.
|
| |
Nature,
450,
670-675.
|
|
|
|
|
|
|
I.S.Shin,
K.Nishikawa,
H.Maruyama,
and
S.Ishii
(2006).
Histidine-tagged shiga toxin B subunit binding assay: simple and specific determination of gb3 content in mammalian cells.
|
| |
Chem Pharm Bull (Tokyo),
54,
522-527.
|
|
|
|
|
|
|
J.P.Williams,
D.C.Smith,
B.N.Green,
B.D.Marsden,
K.R.Jennings,
L.M.Roberts,
and
J.H.Scrivens
(2006).
Gas phase characterization of the noncovalent quaternary structure of cholera toxin and the cholera toxin B subunit pentamer.
|
| |
Biophys J,
90,
3246-3254.
|
|
|
|
|
|
|
M.E.Fraser,
M.M.Cherney,
P.Marcato,
G.L.Mulvey,
G.D.Armstrong,
and
M.N.James
(2006).
Binding of adenine to Stx2, the protein toxin from Escherichia coli O157:H7.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
62,
627-630.
|
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PDB code:
|
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|
|
|
|
|
M.J.Smith,
H.M.Carvalho,
A.R.Melton-Celsa,
and
A.D.O'Brien
(2006).
The 13C4 monoclonal antibody that neutralizes Shiga toxin Type 1 (Stx1) recognizes three regions on the Stx1 B subunit and prevents Stx1 from binding to its eukaryotic receptor globotriaosylceramide.
|
| |
Infect Immun,
74,
6992-6998.
|
|
|
|
|
|
|
M.T.Tarragó-Trani,
S.Jiang,
K.C.Harich,
and
B.Storrie
(2006).
Shiga-like toxin subunit B (SLTB)-enhanced delivery of chlorin e6 (Ce6) improves cell killing.
|
| |
Photochem Photobiol,
82,
527-537.
|
|
|
|
|
|
|
C.Welinder-Olsson,
and
B.Kaijser
(2005).
Enterohemorrhagic Escherichia coli (EHEC).
|
| |
Scand J Infect Dis,
37,
405-416.
|
|
|
|
|
|
|
E.N.Kitova,
R.Daneshfar,
P.Marcato,
G.L.Mulvey,
G.Armstrong,
and
J.S.Klassen
(2005).
Stability of the homopentameric B subunits of shiga toxins 1 and 2 in solution and the gas phase as revealed by nanoelectrospray fourier transform ion cyclotron resonance mass spectrometry.
|
| |
J Am Soc Mass Spectrom,
16,
1957-1968.
|
|
|
|
|
|
|
L.M.Harrison,
C.van den Hoogen,
W.C.van Haaften,
and
V.L.Tesh
(2005).
Chemokine expression in the monocytic cell line THP-1 in response to purified shiga toxin 1 and/or lipopolysaccharides.
|
| |
Infect Immun,
73,
403-412.
|
|
|
|
|
|
|
N.Rekha,
S.M.Machado,
C.Narayanan,
A.Krupa,
and
N.Srinivasan
(2005).
Interaction interfaces of protein domains are not topologically equivalent across families within superfamilies: Implications for metabolic and signaling pathways.
|
| |
Proteins,
58,
339-353.
|
|
|
|
|
|
|
P.LaPointe,
X.Wei,
and
J.Gariépy
(2005).
A role for the protease-sensitive loop region of Shiga-like toxin 1 in the retrotranslocation of its A1 domain from the endoplasmic reticulum lumen.
|
| |
J Biol Chem,
280,
23310-23318.
|
|
|
|
|
|
|
P.Marcato,
T.P.Griener,
G.L.Mulvey,
and
G.D.Armstrong
(2005).
Recombinant Shiga toxin B-subunit-keyhole limpet hemocyanin conjugate vaccine protects mice from Shigatoxemia.
|
| |
Infect Immun,
73,
6523-6529.
|
|
|
|
|
|
|
S.Y.Lee,
R.P.Cherla,
I.Caliskan,
and
V.L.Tesh
(2005).
Shiga toxin 1 induces apoptosis in the human myelogenous leukemia cell line THP-1 by a caspase-8-dependent, tumor necrosis factor receptor-independent mechanism.
|
| |
Infect Immun,
73,
5115-5126.
|
|
|
|
|
|
|
L.M.Harrison,
W.C.van Haaften,
and
V.L.Tesh
(2004).
Regulation of proinflammatory cytokine expression by Shiga toxin 1 and/or lipopolysaccharides in the human monocytic cell line THP-1.
|
| |
Infect Immun,
72,
2618-2627.
|
|
|
|
|
|
|
M.E.Fraser,
M.Fujinaga,
M.M.Cherney,
A.R.Melton-Celsa,
E.M.Twiddy,
A.D.O'Brien,
and
M.N.James
(2004).
Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7.
|
| |
J Biol Chem,
279,
27511-27517.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
R.Natarajan,
and
A.D.Linstedt
(2004).
A cycling cis-Golgi protein mediates endosome-to-Golgi traffic.
|
| |
Mol Biol Cell,
15,
4798-4806.
|
|
|
|
|
|
|
I.Basu,
W.A.Ferens,
D.M.Stone,
and
C.J.Hovde
(2003).
Antiviral activity of shiga toxin requires enzymatic activity and is associated with increased permeability of the target cells.
|
| |
Infect Immun,
71,
327-334.
|
|
|
|
|
|
|
R.P.Cherla,
S.Y.Lee,
and
V.L.Tesh
(2003).
Shiga toxins and apoptosis.
|
| |
FEMS Microbiol Lett,
228,
159-166.
|
|
|
|
|
|
|
S.D.Gamage,
J.E.Strasser,
C.L.Chalk,
and
A.A.Weiss
(2003).
Nonpathogenic Escherichia coli can contribute to the production of Shiga toxin.
|
| |
Infect Immun,
71,
3107-3115.
|
|
|
|
|
|
|
P.H.Leung,
J.S.Peiris,
W.W.Ng,
and
W.C.Yam
(2002).
Polyclonal antibodies to glutathione S-transferase--verotoxin subunit a fusion proteins neutralize verotoxins.
|
| |
Clin Diagn Lab Immunol,
9,
687-692.
|
|
|
|
|
|
|
H.Nakajima,
N.Kiyokawa,
Y.U.Katagiri,
T.Taguchi,
T.Suzuki,
T.Sekino,
K.Mimori,
T.Ebata,
M.Saito,
H.Nakao,
T.Takeda,
and
J.Fujimoto
(2001).
Kinetic analysis of binding between Shiga toxin and receptor glycolipid Gb3Cer by surface plasmon resonance.
|
| |
J Biol Chem,
276,
42915-42922.
|
|
|
|
|
|
|
J.Gariépy
(2001).
The use of Shiga-like toxin 1 in cancer therapy.
|
| |
Crit Rev Oncol Hematol,
39,
99.
|
|
|
|
|
|
|
M.R.Bray,
S.Bisland,
S.Perampalam,
W.M.Lim,
and
J.Gariépy
(2001).
Probing the surface of eukaryotic cells using combinatorial toxin libraries.
|
| |
Curr Biol,
11,
697-701.
|
|
|
|
|
|
|
V.M.Wolski,
A.M.Soltyk,
and
J.L.Brunton
(2001).
Mouse toxicity and cytokine release by verotoxin 1 B subunit mutants.
|
| |
Infect Immun,
69,
579-583.
|
|
|
|
|
|
|
E.Fan,
E.A.Merritt,
C.L.Verlinde,
and
W.G.Hol
(2000).
AB(5) toxins: structures and inhibitor design.
|
| |
Curr Opin Struct Biol,
10,
680-686.
|
|
|
|
|
|
|
H.Ling,
N.S.Pannu,
A.Boodhoo,
G.D.Armstrong,
C.G.Clark,
J.L.Brunton,
and
R.J.Read
(2000).
A mutant Shiga-like toxin IIe bound to its receptor Gb(3): structure of a group II Shiga-like toxin with altered binding specificity.
|
| |
Structure,
8,
253-264.
|
|
|
PDB codes:
|
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|
|
|
|
|
|
K.Sandvig,
and
B.van Deurs
(2000).
Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives.
|
| |
EMBO J,
19,
5943-5950.
|
|
|
|
|
|
|
M.Brigotti,
D.Carnicelli,
P.Accorsi,
S.Rizzi,
L.Montanaro,
and
S.Sperti
(2000).
4-Aminopyrazolo[3,4-d]pyrimidine (4-APP) as a novel inhibitor of the RNA and DNA depurination induced by Shiga toxin 1.
|
| |
Nucleic Acids Res,
28,
2383-2388.
|
|
|
|
|
|
|
H.Nakao,
N.Kiyokawa,
J.Fujimoto,
S.Yamasaki,
and
T.Takeda
(1999).
Monoclonal antibody to Shiga toxin 2 which blocks receptor binding and neutralizes cytotoxicity.
|
| |
Infect Immun,
67,
5717-5722.
|
|
|
|
|
|
|
D.B.Lacy,
and
R.C.Stevens
(1998).
Unraveling the structures and modes of action of bacterial toxins.
|
| |
Curr Opin Struct Biol,
8,
778-784.
|
|
|
|
|
|
|
H.Ling,
A.Boodhoo,
B.Hazes,
M.D.Cummings,
G.D.Armstrong,
J.L.Brunton,
and
R.J.Read
(1998).
Structure of the shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3.
|
| |
Biochemistry,
37,
1777-1788.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.C.Paton,
and
A.W.Paton
(1998).
Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections.
|
| |
Clin Microbiol Rev,
11,
450-479.
|
|
|
|
|
|
|
J.K.Suh,
C.J.Hovde,
and
J.D.Robertus
(1998).
Shiga toxin attacks bacterial ribosomes as effectively as eucaryotic ribosomes.
|
| |
Biochemistry,
37,
9394-9398.
|
|
|
|
|
|
|
M.L.Suhan,
and
C.J.Hovde
(1998).
Disruption of an internal membrane-spanning region in Shiga toxin 1 reduces cytotoxicity.
|
| |
Infect Immun,
66,
5252-5259.
|
|
|
|
|
|
|
C.Lesieur,
B.Vécsey-Semjén,
L.Abrami,
M.Fivaz,
and
F.Gisou van der Goot
(1997).
Membrane insertion: The strategies of toxins (review).
|
| |
Mol Membr Biol,
14,
45-64.
|
|
|
|
|
|
|
C.R.MacKenzie,
T.Hirama,
K.K.Lee,
E.Altman,
and
N.M.Young
(1997).
Quantitative analysis of bacterial toxin affinity and specificity for glycolipid receptors by surface plasmon resonance.
|
| |
J Biol Chem,
272,
5533-5538.
|
|
|
|
|
|
|
D.J.Bast,
J.L.Brunton,
M.A.Karmali,
and
S.E.Richardson
(1997).
Toxicity and immunogenicity of a verotoxin 1 mutant with reduced globotriaosylceramide receptor binding in rabbits.
|
| |
Infect Immun,
65,
2019-2028.
|
|
|
|
|
|
|
J.Rossjohn,
J.T.Buckley,
B.Hazes,
A.G.Murzin,
R.J.Read,
and
M.W.Parker
(1997).
Aerolysin and pertussis toxin share a common receptor-binding domain.
|
| |
EMBO J,
16,
3426-3434.
|
|
|
|
|
|
|
L.Johannes,
D.Tenza,
C.Antony,
and
B.Goud
(1997).
Retrograde transport of KDEL-bearing B-fragment of Shiga toxin.
|
| |
J Biol Chem,
272,
19554-19561.
|
|
|
|
|
|
|
L.M.Skinner,
and
M.P.Jackson
(1997).
Investigation of ribosome binding by the Shiga toxin A1 subunit, using competition and site-directed mutagenesis.
|
| |
J Bacteriol,
179,
1368-1374.
|
|
|
|
|
|
|
O.Garred,
E.Dubinina,
A.Polesskaya,
S.Olsnes,
J.Kozlov,
and
K.Sandvig
(1997).
Role of the disulfide bond in Shiga toxin A-chain for toxin entry into cells.
|
| |
J Biol Chem,
272,
11414-11419.
|
|
|
|
|
|
|
A.R.Melton-Celsa,
S.C.Darnell,
and
A.D.O'Brien
(1996).
Activation of Shiga-like toxins by mouse and human intestinal mucus correlates with virulence of enterohemorrhagic Escherichia coli O91:H21 isolates in orally infected, streptomycin-treated mice.
|
| |
Infect Immun,
64,
1569-1576.
|
|
|
|
|
|
|
C.A.Lingwood
(1996).
Aglycone modulation of glycolipid receptor function.
|
| |
Glycoconj J,
13,
495-503.
|
|
|
|
|
|
|
F.van den Akker,
S.Sarfaty,
E.M.Twiddy,
T.D.Connell,
R.K.Holmes,
and
W.G.Hol
(1996).
Crystal structure of a new heat-labile enterotoxin, LT-IIb.
|
| |
Structure,
4,
665-678.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.T.Saleh,
J.Ferguson,
J.M.Boggs,
and
J.Gariépy
(1996).
Insertion and orientation of a synthetic peptide representing the C-terminus of the A1 domain of Shiga toxin into phospholipid membranes.
|
| |
Biochemistry,
35,
9325-9334.
|
|
|
|
|
|
|
P.G.Nyholm,
G.Magnusson,
Z.Zheng,
R.Norel,
B.Binnington-Boyd,
and
C.A.Lingwood
(1996).
Two distinct binding sites for globotriaosyl ceramide on verotoxins: identification by molecular modelling and confirmation using deoxy analogues and a new glycolipid receptor for all verotoxins.
|
| |
Chem Biol,
3,
263-275.
|
|
|
|
|
|
|
C.Jemal,
J.E.Haddad,
D.Begum,
and
M.P.Jackson
(1995).
Analysis of Shiga toxin subunit association by using hybrid A polypeptides and site-specific mutagenesis.
|
| |
J Bacteriol,
177,
3128-3132.
|
|
|
|
|
|
|
E.A.Merritt,
and
W.G.Hol
(1995).
AB5 toxins.
|
| |
Curr Opin Struct Biol,
5,
165-171.
|
|
|
|
|
|
|
K.A.Karlsson
(1995).
Microbial recognition of target-cell glycoconjugates.
|
| |
Curr Opin Struct Biol,
5,
622-635.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
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only a partial list as not all journals are covered by
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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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