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* Residue conservation analysis
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DOI no:
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Biochemistry
41:13575-13586
(2002)
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PubMed id:
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Molecular recognition of oligosaccharide epitopes by a monoclonal Fab specific for Shigella flexneri Y lipopolysaccharide: X-ray structures and thermodynamics.
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N.K.Vyas,
M.N.Vyas,
M.C.Chervenak,
M.A.Johnson,
B.M.Pinto,
D.R.Bundle,
F.A.Quiocho.
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ABSTRACT
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The antigenic recognition of Shigella flexneri O-polysaccharide, which consists
of a repeating unit ABCD
[-->2)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-beta-D-GlcpNAc-(1-->],
by the monoclonal antibody SYA/J6 (IgG3, kappa) has been investigated by
crystallographic analysis of the Fab domain and its two complexes with two
antigen segments (a pentasaccharide Rha A-Rha B-Rha C-GlcNAc D-Rha A' and a
modified trisaccharide Rha B-Rha C-GlcNAc D in which Rha C* is missing a C2-OH
group). These complex structures, the first for a Fab specific for a periodic
linear heteropolysaccharide, reveal a binding site groove (between the V(H) and
V(L) domains) that makes polar and nonpolar contacts with all the sugar residues
of the pentasaccharide. Both main-chain and side-chain atoms of the Fab are used
in ligand binding. The charged side chain of Glu H50 of CDR H2 forms crucial
hydrogen bonds to GlcNAc of the oligosaccharides. The modified trisaccharide is
more buried and fits more snugly than the pentasaccharide. It also makes as many
contacts (approximately 75) with the Fab as the pentasaccharide, including the
same number of hydrogen bonds (eight, with four being identical). It is further
engaged in more hydrophobic interactions than the pentasaccharide. These three
features favorable to trisaccharide binding are consistent with the observation
of a tighter complex with the trisaccharide than the pentasaccharide.
Thermodynamic data demonstrate that the native tri- to pentasaccharides have
free energies of binding in the range of 6.8-7.4 kcal mol(-1), and all but one
of the hydrogen bonds to individual hydroxyl groups provide no more than
approximately 0.7 kcal mol(-1). They further indicate that hydrophobic
interactions make significant contributions to binding and, as the native
epitope becomes larger across the tri-, tetra-, pentasaccharide series, entropy
contributions to the free energy become dominant.
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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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F.X.Theillet,
C.Simenel,
C.Guerreiro,
A.Phalipon,
L.A.Mulard,
and
M.Delepierre
(2011).
Effects of backbone substitutions on the conformational behavior of Shigella flexneri O-antigens: implications for vaccine strategy.
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Glycobiology,
21,
109-121.
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C.L.Brooks,
R.J.Blackler,
G.Sixta,
P.Kosma,
S.Müller-Loennies,
L.Brade,
T.Hirama,
C.R.MacKenzie,
H.Brade,
and
S.V.Evans
(2010).
The role of CDR H3 in antibody recognition of a synthetic analog of a lipopolysaccharide antigen.
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Glycobiology,
20,
138-147.
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PDB codes:
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C.L.Brooks,
S.Müller-Loennies,
S.N.Borisova,
L.Brade,
P.Kosma,
T.Hirama,
C.R.Mackenzie,
H.Brade,
and
S.V.Evans
(2010).
Antibodies raised against chlamydial lipopolysaccharide antigens reveal convergence in germline gene usage and differential epitope recognition.
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Biochemistry,
49,
570-581.
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PDB codes:
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N.E.van Houten,
K.A.Henry,
G.P.Smith,
and
J.K.Scott
(2010).
Engineering filamentous phage carriers to improve focusing of antibody responses against peptides.
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Vaccine,
28,
2174-2185.
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H.Connaris,
P.R.Crocker,
and
G.L.Taylor
(2009).
Enhancing the Receptor Affinity of the Sialic Acid-binding Domain of Vibrio cholerae Sialidase through Multivalency.
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J Biol Chem,
284,
7339-7351.
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PDB code:
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S.L.Harris,
and
P.Fernsten
(2009).
Thermodynamics and density of binding of a panel of antibodies to high-molecular-weight capsular polysaccharides.
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Clin Vaccine Immunol,
16,
37-42.
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B.Vulliez-Le Normand,
F.A.Saul,
A.Phalipon,
F.Bélot,
C.Guerreiro,
L.A.Mulard,
and
G.A.Bentley
(2008).
Structures of synthetic O-antigen fragments from serotype 2a Shigella flexneri in complex with a protective monoclonal antibody.
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Proc Natl Acad Sci U S A,
105,
9976-9981.
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PDB codes:
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K.N.Kirschner,
A.B.Yongye,
S.M.Tschampel,
J.González-Outeiriño,
C.R.Daniels,
B.L.Foley,
and
R.J.Woods
(2008).
GLYCAM06: A generalizable biomolecular force field. Carbohydrates.
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J Comput Chem,
29,
622-655.
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L.Krishnan,
G.Sahni,
K.J.Kaur,
and
D.M.Salunke
(2008).
Role of antibody paratope conformational flexibility in the manifestation of molecular mimicry.
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Biophys J,
94,
1367-1376.
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PDB code:
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S.Borrelli,
R.B.Hossany,
and
B.M.Pinto
(2008).
Immunological evidence for functional rather than structural mimicry by a Shigella flexneri Y polysaccharide-mimetic peptide.
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Clin Vaccine Immunol,
15,
1106-1114.
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T.K.Dam,
M.Torres,
C.F.Brewer,
and
A.Casadevall
(2008).
Isothermal Titration Calorimetry Reveals Differential Binding Thermodynamics of Variable Region-identical Antibodies Differing in Constant Region for a Univalent Ligand.
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J Biol Chem,
283,
31366-31370.
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M.N.Dharmasena,
D.A.Jewell,
and
R.K.Taylor
(2007).
Development of peptide mimics of a protective epitope of Vibrio cholerae Ogawa O-antigen and investigation of the structural basis of peptide mimicry.
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J Biol Chem,
282,
33805-33816.
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M.J.Clément,
A.Fortuné,
A.Phalipon,
V.Marcel-Peyre,
C.Simenel,
A.Imberty,
M.Delepierre,
and
L.A.Mulard
(2006).
Toward a better understanding of the basis of the molecular mimicry of polysaccharide antigens by peptides: the example of Shigella flexneri 5a.
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J Biol Chem,
281,
2317-2332.
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R.S.McGavin,
and
D.R.Bundle
(2005).
Developing high affinity oligosaccharide inhibitors: conformational pre-organization paired with functional group modification.
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Org Biomol Chem,
3,
2733-2740.
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R.S.McGavin,
R.A.Gagne,
M.C.Chervenak,
and
D.R.Bundle
(2005).
The design, synthesis and evaluation of high affinity macrocyclic carbohydrate inhibitors.
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Org Biomol Chem,
3,
2723-2732.
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U.Krengel,
L.L.Olsson,
C.Martínez,
A.Talavera,
G.Rojas,
E.Mier,
J.Angström,
and
E.Moreno
(2004).
Structure and molecular interactions of a unique antitumor antibody specific for N-glycolyl GM3.
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J Biol Chem,
279,
5597-5603.
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PDB code:
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H.P.Nguyen,
N.O.Seto,
C.R.MacKenzie,
L.Brade,
P.Kosma,
H.Brade,
and
S.V.Evans
(2003).
Germline antibody recognition of distinct carbohydrate epitopes.
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Nat Struct Biol,
10,
1019-1025.
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PDB codes:
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N.K.Vyas,
M.N.Vyas,
M.C.Chervenak,
D.R.Bundle,
B.M.Pinto,
and
F.A.Quiocho
(2003).
Structural basis of peptide-carbohydrate mimicry in an antibody-combining site.
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Proc Natl Acad Sci U S A,
100,
15023-15028.
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PDB code:
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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
