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PDBsum entry 2mpa
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Immune system
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PDB id
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2mpa
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Contents |
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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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Bactericidal antibody recognition of a pora epitope of neisseria meningitidis: crystal structure of a FAB fragment in complex with a fluorescein-Conjugated peptide.
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Authors
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J.M.Van den elsen,
J.N.Herron,
P.Hoogerhout,
J.T.Poolman,
E.Boel,
T.Logtenberg,
J.Wilting,
D.J.Crommelin,
J.Kroon,
P.Gros.
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Ref.
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Proteins, 1997,
29,
113-125.
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PubMed id
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Abstract
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Class 1 outer membrane protein PorA of Neisseria meningitidis is a vaccine
candidate against bacterial meningitis. Antibodies against PorA are able to
induce complement-mediated bacterial killing and thereby play an important role
in protection against meningococcal disease. Bactericidal antibodies are all
directed against variable regions VR1 and VR2 of the PorA sequence,
corresponding to loops 1 and 4 of a two-dimensional topology model of the porin
with eight extracellular loops. We have determined the crystal structure to 2.6
A resolution of the Fab fragment of bactericidal antibody MN12H2 against
meningococcal PorA in complex with a linear fluorescein-conjugated peptide
TKDTNNNL derived from the VR2 sequence of sero-subtype P1.7,16 (residues
180-187) from meningococcal strain H44/76. The peptide folds deeply into the
binding cavity of the Fab molecule in a type I beta-turn, with the minimal P1.16
epitope DTNNN virtually completely buried. The structure reveals H-bonds and van
der Waals interactions with all minimal epitope residues and one essential salt
bridge between Asp-182 of the peptide and His-31 of the MN12H2 light chain. The
key components of the recognition of PorA epitope P1.16 by bactericidal antibody
MN12H2 correspond well with available thermodynamic data from binding studies.
Furthermore, they indicate the structural basis of an increased endemic
incidence of infection by group B meningococci in England and Wales since 1981
associated with the occurrence of an Neisseria meningitidis escape mutant
(strain-MC58). The observed three-dimensional conformation of the peptide
provides a rationale for the development of a synthetic peptide vaccine against
meningococcal disease.
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Secondary reference #1
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Title
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Bactericidal antibody recognition of meningococcal pora by induced fit. Comparison of liganded and unliganded FAB structures.
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Authors
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J.Van den elsen,
L.Vandeputte-Rutten,
J.Kroon,
P.Gros.
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Ref.
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J Biol Chem, 1999,
274,
1495-1501.
[DOI no: ]
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PubMed id
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Figure 3.
Fig. 3. A, relative positions of the variable light and
heavy chains in the dimers of the unliganded Fab and the
Fab-peptide complex. B, conformational differences in hyper
variable loop H3 between the unliganded MN12H2 Fab and the
Fab-peptide complex. C, superposition of the cavity floor
residues of the unliganded and liganded MN12H2 Fabs. For these
figures the corresponding V[L] chains of the monoclinic
unliganded Fab and the liganded Fab structures were overlaid as
a dimer as described in Fig. 2. Light and heavy chain residues
of the liganded Fab are shown in green and magenta. Unliganded
Fab residues and their corresponding backbone positions are
shown in yellow. These figures were produced with MOLSCRIPT and
RASTER3D (30, 31).
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Figure 4.
Fig. 4. Molecular surface areas of the binding site of
the free MN12H2 Fab (A) and the Fab-peptide complex (B). The
surface is colored for electropotential (blue for positive
charge, red for negative charge). The approximate locations of
hypervariable loops and binding site residues are indicated.
This figure was prepared with the program GRASP (32).
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The above figures are
reproduced from the cited reference
with permission from the ASBMB
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