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PDBsum entry 2h1p
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Complex (antibody/peptide)
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PDB id
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2h1p
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Contents |
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219 a.a.
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220 a.a.
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11 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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The three-Dimensional structures of a polysaccharide binding antibody to cryptococcus neoformans and its complex with a peptide from a phage display library: implications for the identification of peptide mimotopes.
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Authors
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A.C.Young,
P.Valadon,
A.Casadevall,
M.D.Scharff,
J.C.Sacchettini.
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Ref.
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J Mol Biol, 1997,
274,
622-634.
[DOI no: ]
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PubMed id
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Abstract
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The three-dimensional structure of 2H1, a protective monoclonal antibody to
Cryptococcus neoformans, has been solved at 2.4 A resolution, in both its
unbound form and in complex with the 12 amino acid residue peptide PA1
(GLQYTPSWMLVG). PA1 was previously identified as a potential mimotope of the
cryptococcal capsular polysaccharide by screening of a phage display peptide
library. Peptide binding is associated with only minor rearrangements of some
side-chains and a small shift in the H2 loop of the antibody. The peptide
assumes a tightly coiled conformation consisting of one inverse gamma-turn and
one type II beta-turn that serves to place the entire peptide motif, consisting
of ThrP5, ProP6, TrpP8, MetP9 and LeuP10, into a depression in the antibody
combining site. A small number of H-bonds between peptide and antibody
contribute to the affinity and specificity. Poor steric complementarity between
PA1 and the antibody heavy chain along with the fact that the majority of the
interactions between 2H1 and PA1 involve van der Waals interactions with the
light chain may explain why this peptide acts as only a partial mimotope of the
capsular polysaccharide epitope.
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Figure 2.
Figure 2. Stereodiagram showing a superposition of the
antibody binding site in the peptide-bound (open circles for
C^α positions and side-chains) and the unbound forms of 2H1
(trace only, no circles). The side-chains of those residues that
differ most between the peptide-bound and the unbound forms of
2H1 are marked, with designating light chain residues and H
designating heavy chain residues. The Figure was produced using
the program MOLSCRIPT [Kraulis 1991].
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Figure 5.
Figure 5. Stereodiagram of the C^α trace of 2H1 showing
H-bonding interactions between the peptide and 2H1. The peptide
is shown in a ball-and-stick representation, with Ala^P2 on the
left, and Gly^P12 on the right. H-bonds are represented as
dotted lines. The side-chains of other residues that make van
der Waals contacts with the peptide are also shown. The Figure
was produced using the program MOLSCRIPT [Kraulis 1991].
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1997,
274,
622-634)
copyright 1997.
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Secondary reference #1
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Title
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Peptide libraries define the fine specificity of anti-Polysaccharide antibodies to cryptococcus neoformans.
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Authors
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P.Valadon,
G.Nussbaum,
L.F.Boyd,
D.H.Margulies,
M.D.Scharff.
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Ref.
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J Mol Biol, 1996,
261,
11-22.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. 2H1 selection. Screening of the peptide
libraries with the monoclonal antibody 2H1 is here
represented as a tree, where circles correspond either to
the original library or to the intermediate libraries, and
arrows indicate the rounds of selection and amplification.
The 2H1 concentration used during each round is
indicated above the corresponding arrow. The under-
lined percentage corresponds to the yield of phage
(number of eluted TU divided by the total number of TU
introduced in the round, in percentage) and the second
number is the percentage of colonies that give a positive
2H1 signal by enhanced immunological screening (see
Materials and Methods).
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Figure 3.
Figure 3. Competitive ELISA with free peptides of
2H1 binding to F514 (a), and binding to cryptococcal
polysaccharide (b). Binding to cryptococcal polysaccha-
ride was done according to the method of Casadevall
et al. (1992b); P315 is an irrelevant control peptide.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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