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Contents |
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214 a.a.
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210 a.a.
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129 a.a.
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* Residue conservation analysis
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PDB id:
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Immune system/hydrolase
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Title:
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Crystal structure of fab fragment of antibody hyhel-26 complexed with lysozyme
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Structure:
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Antibody kappa light chain. Chain: a. Fragment: light chain. Engineered: yes. Other_details: first chain of anti-lysozyme antibody hyhel-26. Immunoglobulin gamma 1 chain. Chain: b. Engineered: yes. Other_details: second chain of anti-lysozyme antibody hyhel-26.
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Source:
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Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Gallus gallus. Chicken. Organism_taxid: 9031. Expressed in: saccharomyces cerevisiae.
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Biol. unit:
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Trimer (from
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Resolution:
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2.10Å
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R-factor:
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0.208
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R-free:
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0.258
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Authors:
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R.A.Mariuzza,Y.Li,H.Li
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Key ref:
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Y.Li
et al.
(2003).
X-ray snapshots of the maturation of an antibody response to a protein antigen.
Nat Struct Biol,
10,
482-488.
PubMed id:
DOI:
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Date:
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09-Dec-02
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Release date:
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03-Jun-03
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PROCHECK
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Headers
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References
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P01837
(IGKC_MOUSE) -
Immunoglobulin kappa constant from Mus musculus
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Seq:
Struc:
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107 a.a.
214 a.a.
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Enzyme class:
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Chain C:
E.C.3.2.1.17
- lysozyme.
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Reaction:
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Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.
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DOI no:
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Nat Struct Biol
10:482-488
(2003)
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PubMed id:
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X-ray snapshots of the maturation of an antibody response to a protein antigen.
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Y.Li,
H.Li,
F.Yang,
S.J.Smith-Gill,
R.A.Mariuzza.
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ABSTRACT
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The process whereby the immune system generates antibodies of higher affinities
during a response to antigen (affinity maturation) is a prototypical example of
molecular evolution. Earlier studies have been confined to antibodies specific
for small molecules (haptens) rather than for proteins. We compare the
structures of four antibodies bound to the same site on hen egg white lysozyme
(HEL) at different stages of affinity maturation. These X-ray snapshots reveal
that binding is enhanced, not through the formation of additional hydrogen bonds
or van der Waals contacts or by an increase in total buried surface, but by
burial of increasing amounts of apolar surface at the expense of polar surface,
accompanied by improved shape complementarity. The increase in hydrophobic
interactions results from highly correlated rearrangements in antibody residues
at the interface periphery, adjacent to the central energetic hot spot. This
first visualization of the maturation of antibodies to protein provides insights
into the evolution of high affinity in other protein-protein interfaces.
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Selected figure(s)
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Figure 1.
Figure 1. Electron density (stereo views) in antibody combining
sites. (a) Density from the final 2F[o] - F[c] map of the H26
-HEL complex in the region of V[H]CDR2 at a resolution of 2.1 Å.
(b) Density from the final 2F[o] - F[c] map of the H8 -HEL
complex in the same region at a resolution of 1.9 Å. Contours
are at 1  .
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Figure 3.
Figure 3. Shape complementarity at antibody -HEL interfaces.
(a) Molecular surface of H26 viewed at the site that interacts
with HEL in the H26 -HEL complex drawn using GRASP37. Regions
with higher S[c] values22, indicating closer topological match
with HEL, are more blue; regions with topologically uncorrelated
surfaces (S[c] = 0) are white. (b) The same view of H26 as
described in a, showing the location of V[H] residues in contact
with HEL. (c) Molecular surface of H8 viewed at the binding site
for HEL in the H8 -HEL complex. As in a, regions with better
geometric fits to the antigen are more blue. (d) The same view
of H8 as described in c, showing V[H] residues that interact
with HEL.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2003,
10,
482-488)
copyright 2003.
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Figures were
selected
by the author.
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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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P.L.Kastritis,
I.H.Moal,
H.Hwang,
Z.Weng,
P.A.Bates,
A.M.Bonvin,
and
J.Janin
(2011).
A structure-based benchmark for protein-protein binding affinity.
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Protein Sci,
20,
482-491.
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A.Malik,
A.Firoz,
V.Jha,
E.Sunderasan,
and
S.Ahmad
(2010).
Modeling the three-dimensional structures of an unbound single-chain variable fragment (scFv) and its hypothetical complex with a Corynespora cassiicola toxin, cassiicolin.
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J Mol Model,
16,
1883-1893.
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B.Li,
L.Zhao,
C.Wang,
H.Guo,
L.Wu,
X.Zhang,
W.Qian,
H.Wang,
and
Y.Guo
(2010).
The protein-protein interface evolution acts in a similar way to antibody affinity maturation.
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J Biol Chem,
285,
3865-3871.
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A.Monegal,
D.Ami,
C.Martinelli,
H.Huang,
M.Aliprandi,
P.Capasso,
C.Francavilla,
G.Ossolengo,
and
A.de Marco
(2009).
Immunological applications of single-domain llama recombinant antibodies isolated from a naïve library.
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Protein Eng Des Sel,
22,
273-280.
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C.A.Velikovsky,
L.Deng,
S.Tasumi,
L.M.Iyer,
M.C.Kerzic,
L.Aravind,
Z.Pancer,
and
R.A.Mariuzza
(2009).
Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen.
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Nat Struct Mol Biol,
16,
725-730.
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PDB codes:
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C.E.Leysath,
A.F.Monzingo,
J.A.Maynard,
J.Barnett,
G.Georgiou,
B.L.Iverson,
and
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(2009).
Crystal structure of the engineered neutralizing antibody M18 complexed to domain 4 of the anthrax protective antigen.
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J Mol Biol,
387,
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PDB codes:
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G.Stewart-Jones,
A.Wadle,
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A.A.Hombach,
V.Cerundolo,
E.Y.Jones,
and
C.Renner
(2009).
Rational development of high-affinity T-cell receptor-like antibodies.
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Proc Natl Acad Sci U S A,
106,
5784-5788.
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PDB codes:
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K.L.Randall,
T.Lambe,
A.Johnson,
B.Treanor,
E.Kucharska,
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J.G.Cyster,
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F.Mackay,
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R.Brink,
C.G.Vinuesa,
F.D.Batista,
R.J.Cornall,
and
C.C.Goodnow
(2009).
Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production.
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Nat Immunol,
10,
1283-1291.
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S.Kiermayr,
K.Stiasny,
and
F.X.Heinz
(2009).
Impact of quaternary organization on the antigenic structure of the tick-borne encephalitis virus envelope glycoprotein E.
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J Virol,
83,
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S.Mohan,
K.Kourentzi,
K.A.Schick,
C.Uehara,
C.A.Lipschultz,
M.Acchione,
M.E.Desantis,
S.J.Smith-Gill,
and
R.C.Willson
(2009).
Association energetics of cross-reactive and specific antibodies.
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Biochemistry,
48,
1390-1398.
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A.Sivasubramanian,
J.A.Maynard,
and
J.J.Gray
(2008).
Modeling the structure of mAb 14B7 bound to the anthrax protective antigen.
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Proteins,
70,
218-230.
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C.A.Smith,
and
T.Kortemme
(2008).
Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction.
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J Mol Biol,
380,
742-756.
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C.A.Thomson,
S.Bryson,
G.R.McLean,
A.L.Creagh,
E.F.Pai,
and
J.W.Schrader
(2008).
Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus.
|
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EMBO J,
27,
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PDB codes:
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F.E.Boas,
and
P.B.Harbury
(2008).
Design of protein-ligand binding based on the molecular-mechanics energy model.
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J Mol Biol,
380,
415-424.
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H.Watanabe,
T.Nakanishi,
M.Umetsu,
and
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(2008).
Human Anti-gold Antibodies: BIOFUNCTIONALIZATION OF GOLD NANOPARTICLES AND SURFACES WITH ANTI-GOLD ANTIBODIES.
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J Biol Chem,
283,
36031-36038.
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K.Kourentzi,
M.Srinivasan,
S.J.Smith-Gill,
and
R.C.Willson
(2008).
Conformational flexibility and kinetic complexity in antibody-antigen interactions.
|
| |
J Mol Recognit,
21,
114-121.
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K.Tsumoto,
A.Yokota,
Y.Tanaka,
M.Ui,
T.Tsumuraya,
I.Fujii,
I.Kumagai,
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H.Oguri,
M.Inoue,
and
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(2008).
Critical contribution of aromatic rings to specific recognition of polyether rings. The case of ciguatoxin CTX3C-ABC and its specific antibody 1C49.
|
| |
J Biol Chem,
283,
12259-12266.
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PDB code:
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N.Krauss,
H.Wessner,
K.Welfle,
H.Welfle,
C.Scholz,
M.Seifert,
K.Zubow,
J.Aÿ,
M.Hahn,
P.Scheerer,
A.Skerra,
and
W.Höhne
(2008).
The structure of the anti-c-myc antibody 9E10 Fab fragment/epitope peptide complex reveals a novel binding mode dominated by the heavy chain hypervariable loops.
|
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Proteins,
73,
552-565.
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PDB codes:
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B.Moza,
A.K.Varma,
R.A.Buonpane,
P.Zhu,
C.A.Herfst,
M.J.Nicholson,
A.K.Wilbuer,
N.P.Seth,
K.W.Wucherpfennig,
J.K.McCormick,
D.M.Kranz,
and
E.J.Sundberg
(2007).
Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1.
|
| |
EMBO J,
26,
1187-1197.
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PDB code:
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I.F.Thorpe,
and
C.L.Brooks
(2007).
Molecular evolution of affinity and flexibility in the immune system.
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Proc Natl Acad Sci U S A,
104,
8821-8826.
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K.Decanniere,
K.Conrath,
R.Loris,
J.Kinne,
S.Muyldermans,
and
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(2006).
Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies.
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Proc Natl Acad Sci U S A,
103,
4586-4591.
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PDB codes:
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E.L.Roggen
(2006).
Recent developments with B-cell epitope identification for predictive studies.
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J Immunotoxicol,
3,
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R.L.Stanfield,
R.A.Brady,
and
M.F.Flajnik
(2006).
First molecular and biochemical analysis of in vivo affinity maturation in an ectothermic vertebrate.
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Proc Natl Acad Sci U S A,
103,
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K.S.Midelfort,
and
K.D.Wittrup
(2006).
Context-dependent mutations predominate in an engineered high-affinity single chain antibody fragment.
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| |
Protein Sci,
15,
324-334.
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L.A.Clark,
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J.Eldredge,
C.Fitch,
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K.J.Hanf,
M.Jarpe,
S.F.Liparoto,
Y.Li,
A.Lugovskoy,
S.Miller,
M.Rushe,
W.Sherman,
K.Simon,
and
H.Van Vlijmen
(2006).
Affinity enhancement of an in vivo matured therapeutic antibody using structure-based computational design.
|
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Protein Sci,
15,
949-960.
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PDB code:
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P.Gupta,
M.Saleemuddin,
and
R.H.Khan
(2006).
Hydrophobic interactions are the prevalent force in bromelain:Fab' complex.
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Biochemistry (Mosc),
71,
S31-S37.
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V.Batori,
E.P.Friis,
H.Nielsen,
and
E.L.Roggen
(2006).
An in silico method using an epitope motif database for predicting the location of antigenic determinants on proteins in a structural context.
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J Mol Recognit,
19,
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E.J.Adams,
Y.H.Chien,
and
K.C.Garcia
(2005).
Structure of a gammadelta T cell receptor in complex with the nonclassical MHC T22.
|
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Science,
308,
227-231.
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PDB code:
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L.C.James,
and
D.S.Tawfik
(2005).
Structure and kinetics of a transient antibody binding intermediate reveal a kinetic discrimination mechanism in antigen recognition.
|
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Proc Natl Acad Sci U S A,
102,
12730-12735.
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PDB code:
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M.C.Demirel,
and
A.M.Lesk
(2005).
Molecular forces in antibody maturation.
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| |
Phys Rev Lett,
95,
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M.Hülsmeyer,
P.Chames,
R.C.Hillig,
R.L.Stanfield,
G.Held,
P.G.Coulie,
C.Alings,
G.Wille,
W.Saenger,
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H.R.Hoogenboom,
and
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(2005).
A major histocompatibility complex-peptide-restricted antibody and t cell receptor molecules recognize their target by distinct binding modes: crystal structure of human leukocyte antigen (HLA)-A1-MAGE-A1 in complex with FAB-HYB3.
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J Biol Chem,
280,
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PDB code:
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M.Ho,
R.J.Kreitman,
M.Onda,
and
I.Pastan
(2005).
In vitro antibody evolution targeting germline hot spots to increase activity of an anti-CD22 immunotoxin.
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J Biol Chem,
280,
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N.S.Srilatha,
P.T.Selvi,
and
G.S.Murthy
(2005).
Epitope mapping from real time kinetic studies - role of crosslinked disulphides and incidental interacting regions in affinity measurements: study with human chorionic gonadotropin and monoclonal antibodies.
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| |
J Biosci,
30,
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R.L.Rich,
and
D.G.Myszka
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Survey of the year 2003 commercial optical biosensor literature.
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| |
J Mol Recognit,
18,
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S.Hogan,
L.Rem,
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I.J.Rondon,
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A.E.Nixon,
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H.R.Hoogenboom,
and
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S.Cho,
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R.A.Mariuzza,
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Structural basis of affinity maturation and intramolecular cooperativity in a protein-protein interaction.
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| |
Structure,
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S.Li,
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P.Kussie,
and
K.M.Ferguson
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Structural basis for inhibition of the epidermal growth factor receptor by cetuximab.
|
| |
Cancer Cell,
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|
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PDB codes:
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|
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Y.Li,
Y.Huang,
C.P.Swaminathan,
S.J.Smith-Gill,
and
R.A.Mariuzza
(2005).
Magnitude of the hydrophobic effect at central versus peripheral sites in protein-protein interfaces.
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| |
Structure,
13,
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|
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PDB codes:
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Y.Li,
Y.Huang,
J.Lue,
J.A.Quandt,
R.Martin,
and
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Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule.
|
| |
EMBO J,
24,
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PDB code:
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A.Cauerhff,
F.A.Goldbaum,
and
B.C.Braden
(2004).
Structural mechanism for affinity maturation of an anti-lysozyme antibody.
|
| |
Proc Natl Acad Sci U S A,
101,
3539-3544.
|
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PDB code:
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B.R.Harvey,
G.Georgiou,
A.Hayhurst,
K.J.Jeong,
B.L.Iverson,
and
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(2004).
Anchored periplasmic expression, a versatile technology for the isolation of high-affinity antibodies from Escherichia coli-expressed libraries.
|
| |
Proc Natl Acad Sci U S A,
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E.De Genst,
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R.Loris,
L.Wyns,
and
S.Muyldermans
(2004).
Chemical basis for the affinity maturation of a camel single domain antibody.
|
| |
J Biol Chem,
279,
53593-53601.
|
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|
PDB code:
|
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|
|
|
|
|
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M.Geva,
M.Eisenstein,
and
L.Addadi
(2004).
Antibody recognition of chiral surfaces. Structural models of antibody complexes with leucine-leucine-tyrosine crystal surfaces.
|
| |
Proteins,
55,
862-873.
|
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W.D.Crill,
and
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(2004).
Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes.
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| |
J Virol,
78,
13975-13986.
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Y.Zhao,
Z.Li,
S.J.Drozd,
Y.Guo,
W.Mourad,
and
H.Li
(2004).
Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex.
|
| |
Structure,
12,
277-288.
|
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|
PDB code:
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H.P.Nguyen,
N.O.Seto,
C.R.MacKenzie,
L.Brade,
P.Kosma,
H.Brade,
and
S.V.Evans
(2003).
Germline antibody recognition of distinct carbohydrate epitopes.
|
| |
Nat Struct Biol,
10,
1019-1025.
|
|
|
PDB codes:
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J.Yang,
C.P.Swaminathan,
Y.Huang,
R.Guan,
S.Cho,
M.C.Kieke,
D.M.Kranz,
R.A.Mariuzza,
and
E.J.Sundberg
(2003).
Dissecting cooperative and additive binding energetics in the affinity maturation pathway of a protein-protein interface.
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| |
J Biol Chem,
278,
50412-50421.
|
|
|
|
|
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|
M.Krogsgaard,
N.Prado,
E.J.Adams,
X.L.He,
D.C.Chow,
D.B.Wilson,
K.C.Garcia,
and
M.M.Davis
(2003).
Evidence that structural rearrangements and/or flexibility during TCR binding can contribute to T cell activation.
|
| |
Mol Cell,
12,
1367-1378.
|
|
|
PDB codes:
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|
S.Mohan,
N.Sinha,
and
S.J.Smith-Gill
(2003).
Modeling the binding sites of anti-hen egg white lysozyme antibodies HyHEL-8 and HyHEL-26: an insight into the molecular basis of antibody cross-reactivity and specificity.
|
| |
Biophys J,
85,
3221-3236.
|
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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
codes are
shown on the right.
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Links
