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PDBsum entry 1ruq
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Immune system
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PDB id
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1ruq
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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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Probing the antibody-Catalyzed water-Oxidation pathway at atomic resolution.
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Authors
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X.Zhu,
P.Wentworth,
A.D.Wentworth,
A.Eschenmoser,
R.A.Lerner,
I.A.Wilson.
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Ref.
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Proc Natl Acad Sci U S A, 2004,
101,
2247-2252.
[DOI no: ]
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PubMed id
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Abstract
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Antibodies can catalyze the generation of hydrogen peroxide (H2O2) from singlet
dioxygen (1O2*) and water via the postulated intermediacy of dihydrogen trioxide
(H2O3) and other trioxygen species. Nine different crystal structures were
determined to elucidate the chemical consequences to the antibody molecule
itself of exposure to such reactive intermediates and to provide insights into
the location on the antibody where these species could be generated. Herein, we
report structural evidence for modifications of two specific antibody residues
within the interfacial region of the variable and constant domains of different
murine antibody antigen-binding fragments (Fabs) by reactive species generated
during the antibody-catalyzed water oxidation process. Crystal structure
analyses of murine Fabs 4C6 and 13G5 after UV-irradiation revealed complex
oxidative modifications to tryptophan L163 and, in 4C6, hydroxylation of the
Cgamma of glutamine H6. These discrete modifications of specific residues add
further support for the "active site" of the water-oxidation pathway
being located within the interfacial region of the constant and variable domains
and highlight the general resistance of the antibody molecule to oxidation by
reactive oxygen species generated during the water-oxidation process.
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Figure 1.
Fig. 1. Stereoview of the crystal structure of 4C6 Fab,
with the C^  trace of the light (L)
and heavy (H) chains colored in light and dark gray,
respectively. The modified tryptophan TrpL163 is highlighted in
red, and other tryptophan residues (such as TrpH97) are colored
green. The modified glutamine residue GlnH6 is also colored red.
All of the figures were generated in BOBSCRIPT (12) and rendered
in RASTER3D (13).
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Figure 4.
Fig. 4. Fourier electron density maps showing TrpL163 in
13G5 Fab for UV-irradiated data set H and native control data
set I. For a and b, the tryptophan residue was refined as
tryptophan, whereas for control (c and d), the tryptophan
residue was refined as alanine to avoid model bias. (a) 2F[o] -
F[c] maps (blue), contoured at 1.0  .(b) F[o] - F[c] maps,
contoured at 3.0 (green) and -3.0 (red).
(c)2F[o] - F[c] maps (blue), contoured at 0.8 .(d)
F[o] - F[c] maps, contoured at 3.0 (green).
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Secondary reference #1
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Title
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An antibody exo diels-Alderase inhibitor complex at 1.95 angstrom resolution.
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Authors
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A.Heine,
E.A.Stura,
J.T.Yli-Kauhaluoma,
C.Gao,
Q.Deng,
B.R.Beno,
K.N.Houk,
K.D.Janda,
I.A.Wilson.
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Ref.
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Science, 1998,
279,
1934-1940.
[DOI no: ]
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PubMed id
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Figure 4.
Fig. 4. Specific interactions of 9 with side chains of the
Fab 13G5 in the antibody-antigen complex. Three hydrogen bonds
are formed with Fab residues TyrL36, AspH50, and AsnL91. In
addition, a water molecule O87 is in close contact to ferrocene
9. The hydrogen-bonding network in the Fab combining site that
orients the side chains of TyrL36, AspH50, and AsnL91 in
position to form hydrogen bonds with 9 are shown in (B). For
AsnL91, this network is extended over three residues. Oxygen
atoms are^ shown in red and nitrogen atoms in blue. Figures 4
and 5 were^ produced with XP (31).
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Figure 8.
Fig. 8. Favored orientations for each of the four isomeric
transition states in antibody 13G5 predicted by AUTODOCK: (A)
(3R,4R)-exo, (B) (3S,4S)-exo, (C) (3R,4S)-endo, and (D)
(3S,4R)-endo. The lowest energy structures in (A), (C), and (D),
and the second lowest in (B) are shown. Only the transition
states of the reaction (Fig. 1) and the interacting side chains
that form hydrogen bonds in the crystal structure of the
ferrocenyl inhibitor are shown for clarity. Only in the exo
forms are all three hydrogen bonds made that are observed in the
crystal structure^ of the inhibitor-Fab complex.
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The above figures are
reproduced from the cited reference
with permission from the AAAs
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