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* Residue conservation analysis
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J Mol Biol
241:534-556
(1994)
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PubMed id:
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Crystal structure of a peptide complex of anti-influenza peptide antibody Fab 26/9. Comparison of two different antibodies bound to the same peptide antigen.
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M.E.Churchill,
E.A.Stura,
C.Pinilla,
J.R.Appel,
R.A.Houghten,
D.H.Kono,
R.S.Balderas,
G.G.Fieser,
U.Schulze-Gahmen,
I.A.Wilson.
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ABSTRACT
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The three-dimensional structure of the complex of a second anti-peptide antibody
(Fab 26/9) that recognizes the same six-residue epitope of an immunogenic
peptide from influenza virus hemagglutinin (HA1; 75-110) as Fab 17/9 with the
peptide has been determined at 2.8 A resolution. The amino acid sequence of the
variable region of the 26/9 antibody differs in 24 positions from that of 17/9,
the first antibody in this series for which several ligand-bound and free
structures have been determined and refined. Comparison of the 26/9-peptide with
the 17/9-peptide complex structures shows that the two Fabs are very similar
(r.m.s.d. 0.5 to 0.8 A) and that the peptide antigen (101-107) has virtually the
same conformation (r.m.s.d. 0.3 to 0.8 A) when bound to both antibodies. A
sequence difference in the 26/9 binding pocket (L94; His in 26/9, Asn in 17/9)
results in an interaction with a bound water molecule that is not seen in the
17/9 structures. Epitope mapping shows that the relative specificity of 26/9 and
17/9 antibodies for individual positions of the peptide antigen are slightly
different. Amino acid substitutions in the peptide, particularly at position
SerP107, are tolerated to different extents by 17/9 and 26/9. Structural and
sequence analysis suggests that amino acid differences near the peptide-binding
site are responsible for altering slightly the specificity of 26/9 for three
peptide residues and illustrates how amino acid substitutions can modify
antibody-antigen interactions and thereby modulate antibody specificity.
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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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J.Feng,
U.Gulati,
X.Zhang,
W.A.Keitel,
D.M.Thompson,
J.A.James,
L.F.Thompson,
and
G.M.Air
(2009).
Antibody quantity versus quality after influenza vaccination.
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Vaccine,
27,
6358-6362.
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R.Pantophlet,
M.Wang,
R.O.Aguilar-Sino,
and
D.R.Burton
(2009).
The human immunodeficiency virus type 1 envelope spike of primary viruses can suppress antibody access to variable regions.
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J Virol,
83,
1649-1659.
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J.A.Greenbaum,
P.H.Andersen,
M.Blythe,
H.H.Bui,
R.E.Cachau,
J.Crowe,
M.Davies,
A.S.Kolaskar,
O.Lund,
S.Morrison,
B.Mumey,
Y.Ofran,
J.L.Pellequer,
C.Pinilla,
J.V.Ponomarenko,
G.P.Raghava,
M.H.van Regenmortel,
E.L.Roggen,
A.Sette,
A.Schlessinger,
J.Sollner,
M.Zand,
and
B.Peters
(2007).
Towards a consensus on datasets and evaluation metrics for developing B-cell epitope prediction tools.
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J Mol Recognit,
20,
75-82.
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P.J.Cachia,
and
R.S.Hodges
(2003).
Synthetic peptide vaccine and antibody therapeutic development: prevention and treatment of Pseudomonas aeruginosa.
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Biopolymers,
71,
141-168.
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M.Ferrer,
B.J.Sullivan,
K.L.Godbout,
E.Burke,
H.S.Stump,
J.Godoy,
A.Golden,
A.T.Profy,
and
M.R.van Schravendijk
(1999).
Structural and functional characterization of an epitope in the conserved C-terminal region of HIV-1 gp120.
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J Pept Res,
54,
32-42.
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S.Vasudevan,
T.Tsuruo,
and
D.R.Rose
(1998).
Mode of binding of anti-P-glycoprotein antibody MRK-16 to its antigen. A crystallographic and molecular modeling study.
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J Biol Chem,
273,
25413-25419.
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PDB code:
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J.A.Hubbard,
D.P.Raleigh,
J.R.Bonnerjea,
and
C.M.Dobson
(1997).
Identification of the epitopes of calcitonin gene-related peptide (CGRP) for two anti-CGRP monoclonal antibodies by 2D NMR.
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Protein Sci,
6,
1945-1952.
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J.R.Appel,
J.Buencamino,
R.A.Houghten,
and
C.Pinilla
(1996).
Exploring antibody polyspecificity using synthetic combinatorial libraries.
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Mol Divers,
2,
29-34.
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J.W.Slootstra,
W.C.Puijk,
G.J.Ligtvoet,
J.P.Langeveld,
and
R.H.Meloen
(1996).
Structural aspects of antibody-antigen interaction revealed through small random peptide libraries.
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Mol Divers,
1,
87-96.
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L.F.Wang,
A.D.Hyatt,
P.L.Whiteley,
M.Andrew,
J.K.Li,
and
B.T.Eaton
(1996).
Topography and immunogenicity of bluetongue virus VP7 epitopes.
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Arch Virol,
141,
111-123.
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E.Warbrick,
D.P.Lane,
D.M.Glover,
and
L.S.Cox
(1995).
A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen.
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Curr Biol,
5,
275-282.
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G.Siligardi,
and
A.F.Drake
(1995).
The importance of extended conformations and, in particular, the PII conformation for the molecular recognition of peptides.
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Biopolymers,
37,
281-292.
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R.L.Stanfield,
and
I.A.Wilson
(1995).
Protein-peptide interactions.
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Curr Opin Struct Biol,
5,
103-113.
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I.A.Wilson,
and
R.L.Stanfield
(1994).
Antibody-antigen interactions: new structures and new conformational changes.
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Curr Opin Struct Biol,
4,
857-867.
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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
code is
shown on the right.
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Links
