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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Structural analysis of the sialyltransferase cstii from campylobacter jejuni in complex with a substrate analogue, cmp-3fneuac.
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Structure:
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Alpha-2,3/8-sialyltransferase. Chain: a, b, c, d. Engineered: yes. Mutation: yes
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Source:
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Campylobacter jejuni. Organism_taxid: 197. Gene: cst. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
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Biol. unit:
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Tetramer (from
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Resolution:
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1.80Å
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R-factor:
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0.217
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R-free:
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0.248
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Authors:
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C.P.Chiu,A.G.Watts,L.L.Lairson,M.Gilbert,D.Lim,W.W.Wakarchuk, S.G.Withers,N.C.Strynadka
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Key ref:
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C.P.Chiu
et al.
(2004).
Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog.
Nat Struct Mol Biol,
11,
163-170.
PubMed id:
DOI:
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Date:
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01-Dec-03
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Release date:
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03-Feb-04
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PROCHECK
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Headers
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References
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DOI no:
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Nat Struct Mol Biol
11:163-170
(2004)
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PubMed id:
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Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog.
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C.P.Chiu,
A.G.Watts,
L.L.Lairson,
M.Gilbert,
D.Lim,
W.W.Wakarchuk,
S.G.Withers,
N.C.Strynadka.
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ABSTRACT
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Sialic acid terminates oligosaccharide chains on mammalian and microbial cell
surfaces, playing critical roles in recognition and adherence. The enzymes that
transfer the sialic acid moiety from cytidine-5'-monophospho-N-acetyl-neuraminic
acid (CMP-NeuAc) to the terminal positions of these key glycoconjugates are
known as sialyltransferases. Despite their important biological roles, little is
understood about the mechanism or molecular structure of these
membrane-associated enzymes. We report the first structure of a
sialyltransferase, that of CstII from Campylobacter jejuni, a highly prevalent
foodborne pathogen. Our structural, mutagenesis and kinetic data provide support
for a novel mode of substrate binding and glycosyl transfer mechanism, including
essential roles of a histidine (general base) and two tyrosine residues
(coordination of the phosphate leaving group). This work provides a framework
for understanding the activity of several sialyltransferases, from bacterial to
human, and for the structure-based design of specific inhibitors.
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Selected figure(s)
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Figure 1.
Figure 1. Reaction scheme of CstII. The bond created in the
monofunctional and binfunctional reaction is highlighted by a
green circle.
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Figure 2.
Figure 2. The overall architecture of CstII  32.
(a) Arrangement of the CstII  32
tetramer. Each monomer is colored differentially. CMP-3FNeuAc is
shown as a stick representation in a magenta color, indicating
the location of the catalytic center. (b) View of CstII 32
monomer showing the N-terminal domain and the lid domain with
bound donor sugar analog. CMP-3FNeuAc is depicted in a red stick
representation. The N terminus, C terminus, individual strands
and individual helices are labeled.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2004,
11,
163-170)
copyright 2004.
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Figures were
selected
by an automated process.
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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.Audry,
C.Jeanneau,
A.Imberty,
A.Harduin-Lepers,
P.Delannoy,
and
C.Breton
(2011).
Current trends in the structure-activity relationships of sialyltransferases.
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Glycobiology,
21,
716-726.
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T.Lindhout,
U.Iqbal,
L.M.Willis,
A.N.Reid,
J.Li,
X.Liu,
M.Moreno,
and
W.W.Wakarchuk
(2011).
Site-specific enzymatic polysialylation of therapeutic proteins using bacterial enzymes.
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Proc Natl Acad Sci U S A,
108,
7397-7402.
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G.K.Wagner,
and
T.Pesnot
(2010).
Glycosyltransferases and their assays.
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Chembiochem,
11,
1939-1949.
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S.F.Hansen,
E.Bettler,
A.Rinnan,
S.B.Engelsen,
and
C.Breton
(2010).
Exploring genomes for glycosyltransferases.
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Mol Biosyst,
6,
1773-1781.
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X.Chen,
and
A.Varki
(2010).
Advances in the biology and chemistry of sialic acids.
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ACS Chem Biol,
5,
163-176.
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|
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|
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Y.Kushi,
H.Kamimiya,
H.Hiratsuka,
H.Nozaki,
H.Fukui,
M.Yanagida,
M.Hashimoto,
K.Nakamura,
S.Watarai,
T.Kasama,
H.Kajiwara,
and
T.Yamamoto
(2010).
Sialyltransferases of marine bacteria efficiently utilize glycosphingolipid substrates.
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Glycobiology,
20,
187-198.
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F.V.Rao,
J.R.Rich,
B.Rakić,
S.Buddai,
M.F.Schwartz,
K.Johnson,
C.Bowe,
W.W.Wakarchuk,
S.Defrees,
S.G.Withers,
and
N.C.Strynadka
(2009).
Structural insight into mammalian sialyltransferases.
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Nat Struct Mol Biol,
16,
1186-1188.
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PDB codes:
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J.C.Paulson,
and
C.Rademacher
(2009).
Glycan terminator.
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Nat Struct Mol Biol,
16,
1121-1122.
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K.Kaida,
T.Ariga,
and
R.K.Yu
(2009).
Antiganglioside antibodies and their pathophysiological effects on Guillain-Barré syndrome and related disorders--a review.
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Glycobiology,
19,
676-692.
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M.G.Szczepina,
R.B.Zheng,
G.C.Completo,
T.L.Lowary,
and
B.M.Pinto
(2009).
STD-NMR studies suggest that two acceptor substrates for GlfT2, a bifunctional galactofuranosyltransferase required for the biosynthesis of Mycobacterium tuberculosis arabinogalactan, compete for the same binding site.
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Chembiochem,
10,
2052-2059.
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P.Zhang,
A.J.Zuccolo,
W.Li,
R.B.Zheng,
and
C.C.Ling
(2009).
Probing a sialyltransferase's recognition domain to prepare alpha(2,8)-linked oligosialosides and analogs.
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Chem Commun (Camb),
(),
4233-4235.
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S.Liu,
L.Meng,
K.W.Moremen,
and
J.H.Prestegard
(2009).
Nuclear magnetic resonance structural characterization of substrates bound to the alpha-2,6-sialyltransferase, ST6Gal-I.
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Biochemistry,
48,
11211-11219.
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T.J.Morley,
L.M.Willis,
C.Whitfield,
W.W.Wakarchuk,
and
S.G.Withers
(2009).
A new sialidase mechanism: bacteriophage K1F endo-sialidase is an inverting glycosidase.
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J Biol Chem,
284,
17404-17410.
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A.Buschiazzo,
and
P.M.Alzari
(2008).
Structural insights into sialic acid enzymology.
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Curr Opin Chem Biol,
12,
565-572.
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J.A.Alfaro,
R.B.Zheng,
M.Persson,
J.A.Letts,
R.Polakowski,
Y.Bai,
S.N.Borisova,
N.O.Seto,
T.L.Lowary,
M.M.Palcic,
and
S.V.Evans
(2008).
ABO(H) blood group A and B glycosyltransferases recognize substrate via specific conformational changes.
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J Biol Chem,
283,
10097-10108.
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PDB codes:
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J.Cheng,
H.Yu,
K.Lau,
S.Huang,
H.A.Chokhawala,
Y.Li,
V.K.Tiwari,
and
X.Chen
(2008).
Multifunctionality of Campylobacter jejuni sialyltransferase CstII: characterization of GD3/GT3 oligosaccharide synthase, GD3 oligosaccharide sialidase, and trans-sialidase activities.
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Glycobiology,
18,
686-697.
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L.L.Lairson,
B.Henrissat,
G.J.Davies,
and
S.G.Withers
(2008).
Glycosyltransferases: structures, functions, and mechanisms.
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Annu Rev Biochem,
77,
521-555.
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R.Louwen,
A.Heikema,
A.van Belkum,
A.Ott,
M.Gilbert,
W.Ang,
H.P.Endtz,
M.P.Bergman,
and
E.E.Nieuwenhuis
(2008).
The sialylated lipooligosaccharide outer core in Campylobacter jejuni is an important determinant for epithelial cell invasion.
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Infect Immun,
76,
4431-4438.
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S.Takashima
(2008).
Characterization of mouse sialyltransferase genes: their evolution and diversity.
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Biosci Biotechnol Biochem,
72,
1155-1167.
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X.Wang,
T.Weldeghiorghis,
G.Zhang,
B.Imperiali,
and
J.H.Prestegard
(2008).
Solution structure of Alg13: the sugar donor subunit of a yeast N-acetylglucosamine transferase.
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Structure,
16,
965-975.
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PDB code:
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F.Freiberger,
H.Claus,
A.Günzel,
I.Oltmann-Norden,
J.Vionnet,
M.Mühlenhoff,
U.Vogel,
W.F.Vann,
R.Gerardy-Schahn,
and
K.Stummeyer
(2007).
Biochemical characterization of a Neisseria meningitidis polysialyltransferase reveals novel functional motifs in bacterial sialyltransferases.
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Mol Microbiol,
65,
1258-1275.
|
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H.Tsukamoto,
Y.Takakura,
and
T.Yamamoto
(2007).
Purification, cloning, and expression of an alpha/beta-galactoside alpha-2,3-sialyltransferase from a luminous marine bacterium, Photobacterium phosphoreum.
|
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J Biol Chem,
282,
29794-29802.
|
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L.L.Lairson,
W.W.Wakarchuk,
and
S.G.Withers
(2007).
Alternative donor substrates for inverting and retaining glycosyltransferases.
|
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Chem Commun (Camb),
(),
365-367.
|
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|
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|
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S.Liu,
A.Venot,
L.Meng,
F.Tian,
K.W.Moremen,
G.J.Boons,
and
J.H.Prestegard
(2007).
Spin-labeled analogs of CMP-NeuAc as NMR probes of the alpha-2,6-sialyltransferase ST6Gal I.
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Chem Biol,
14,
409-418.
|
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Y.Li,
M.Sun,
S.Huang,
H.Yu,
H.A.Chokhawala,
V.Thon,
and
X.Chen
(2007).
The Hd0053 gene of Haemophilus ducreyi encodes an alpha2,3-sialyltransferase.
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Biochem Biophys Res Commun,
361,
555-560.
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A.Aharoni,
K.Thieme,
C.P.Chiu,
S.Buchini,
L.L.Lairson,
H.Chen,
N.C.Strynadka,
W.W.Wakarchuk,
and
S.G.Withers
(2006).
High-throughput screening methodology for the directed evolution of glycosyltransferases.
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Nat Methods,
3,
609-614.
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B.Ma,
G.F.Audette,
S.Lin,
M.M.Palcic,
B.Hazes,
and
D.E.Taylor
(2006).
Purification, kinetic characterization, and mapping of the minimal catalytic domain and the key polar groups of Helicobacter pylori alpha-(1,3/1,4)-fucosyltransferases.
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J Biol Chem,
281,
6385-6394.
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E.T.Larson,
D.Reiter,
M.Young,
and
C.M.Lawrence
(2006).
Structure of A197 from Sulfolobus turreted icosahedral virus: a crenarchaeal viral glycosyltransferase exhibiting the GT-A fold.
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J Virol,
80,
7636-7644.
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PDB code:
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J.E.Pak,
P.Arnoux,
S.Zhou,
P.Sivarajah,
M.Satkunarajah,
X.Xing,
and
J.M.Rini
(2006).
X-ray crystal structure of leukocyte type core 2 beta1,6-N-acetylglucosaminyltransferase. Evidence for a convergence of metal ion-independent glycosyltransferase mechanism.
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J Biol Chem,
281,
26693-26701.
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PDB codes:
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L.L.Lairson,
A.G.Watts,
W.W.Wakarchuk,
and
S.G.Withers
(2006).
Using substrate engineering to harness enzymatic promiscuity and expand biological catalysis.
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Nat Chem Biol,
2,
724-728.
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M.S.Sujatha,
and
P.V.Balaji
(2006).
Fold-recognition and comparative modeling of human alpha2,3-sialyltransferases reveal their sequence and structural similarities to CstII from Campylobacter jejuni.
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BMC Struct Biol,
6,
9.
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R.K.Yu,
S.Usuki,
and
T.Ariga
(2006).
Ganglioside molecular mimicry and its pathological roles in Guillain-Barré syndrome and related diseases.
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Infect Immun,
74,
6517-6527.
|
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J.Flint,
E.Taylor,
M.Yang,
D.N.Bolam,
L.E.Tailford,
C.Martinez-Fleites,
E.J.Dodson,
B.G.Davis,
H.J.Gilbert,
and
G.J.Davies
(2005).
Structural dissection and high-throughput screening of mannosylglycerate synthase.
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Nat Struct Mol Biol,
12,
608-614.
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PDB codes:
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P.K.Qasba,
B.Ramakrishnan,
and
E.Boeggeman
(2005).
Substrate-induced conformational changes in glycosyltransferases.
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Trends Biochem Sci,
30,
53-62.
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P.C.Godschalk,
A.P.Heikema,
M.Gilbert,
T.Komagamine,
C.W.Ang,
J.Glerum,
D.Brochu,
J.Li,
N.Yuki,
B.C.Jacobs,
A.van Belkum,
and
H.P.Endtz
(2004).
The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome.
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J Clin Invest,
114,
1659-1665.
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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
codes are
shown on the right.
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Links
