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PDBsum entry 1c08
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Immune system/hydrolase
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PDB id
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1c08
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Contents |
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107 a.a.
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114 a.a.
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129 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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Crystal structure of anti-Hen egg white lysozyme antibody (hyhel-10) fv-Antigen complex. Local structural changes in the protein antigen and water-Mediated interactions of fv-Antigen and light chain-Heavy chain interfaces.
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Authors
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H.Kondo,
M.Shiroishi,
M.Matsushima,
K.Tsumoto,
I.Kumagai.
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Ref.
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J Biol Chem, 1999,
274,
27623-27631.
[DOI no: ]
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PubMed id
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Abstract
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In order to address the recognition mechanism of the fragments of antibody
variable regions, termed Fv, toward their target antigen, an x-ray crystal
structure of an anti-hen egg white lysozyme antibody (HyHEL-10) Fv fragment
complexed with its cognate antigen, hen egg white lysozyme (HEL), was solved at
2.3 A. The overall structure of the complex is similar to that reported in a
previous article dealing with the Fab fragment-HEL complex (PDB ID code,).
However, the areas of Fv covered by HEL upon complex formation increased by
about 100 A(2) in comparison with the Fab-HEL complex, and two local structural
differences were observed in the heavy chain of the variable region (VH). In
addition, small but significant local structural changes were observed in the
antigen, HEL. The x-ray data permitted the identification of two water molecules
between the VH and HEL and six water molecules retained in the interface between
the antigen and the light chain complementarity determining regions (CDRs) 2 and
3 (CDR-L2 and CDR-L3). These water molecules bridge the antigen-antibody
interface through hydrogen bond formation in the VL-HEL interface. Eleven water
molecules were found to complete the imperfect VH-VL interface, suggesting that
solvent molecules mediate the stabilization of interaction between variable
regions. These results suggest that the unfavorable effect of deletion of
constant regions on the antigen-antibody interaction is compensated by an
increase in favorable interactions, including structural changes in the
antigen-antibody interface and solvent-mediated hydrogen bond formation upon
complex formation, which may lead to a minimum decreased affinity of the
antibody Fv fragment toward its antigen.
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Figure 2.
Fig. 2. Schematic model of HyHEL-10 Fv-HEL complex. The
Fv-HEL complex model, of which the C  coordinates
of HEL are superimposed on the C coordinates
of HEL complexed with Fab, is superimposed on the Fab model
(gray). This model was produced with the programs MOLSCRIPT (69)
and Raster3D (70). VH, cyan; VL, green; HEL, magenta.
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Figure 6.
Fig. 6. Comparison of side chains and main chains in Fv
with those in Fab. Fab is represented with light gray sticks and
Fv by dark gray sticks. A, CDR-H1 loop. B, CDR-H3 loop. The
water molecule of Fab exists near HAsp-96 of Fv. The C backbone of
VL is represented with a thick stick. The figure was generated
using WebLab Viewer (MSI).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(1999,
274,
27623-27631)
copyright 1999.
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