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107 a.a.
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116 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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Complex (immunoglobulin/hydrolase)
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Title:
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Fv mutant y(b 32)a (vh domain) of mouse monoclonal antibody d1.3 complexed with hen egg white lysozyme
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Structure:
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Monoclonal antibody d1.3. Chain: a. Engineered: yes. Mutation: yes. Monoclonal antibody d1.3. Chain: b. Engineered: yes. Mutation: yes. Lysozyme.
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Source:
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Mus musculus. House mouse. Organism_taxid: 10090. Organ: egg. Expressed in: escherichia coli. Expression_system_taxid: 562. Gallus gallus. Chicken. Organism_taxid: 9031.
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Biol. unit:
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Dimer (from
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Resolution:
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Authors:
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B.A.Fields,R.J.Poljak,R.A.Mariuzza
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Key ref:
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B.A.Fields
et al.
(1996).
Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme.
Biochemistry,
35,
15494-15503.
PubMed id:
DOI:
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Date:
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23-Oct-96
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Release date:
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23-Dec-96
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PROCHECK
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Headers
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References
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P01635
(KV5A3_MOUSE) -
Immunoglobulin kappa chain variable 12-41 (Fragment) from Mus musculus
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Seq:
Struc:
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115 a.a.
107 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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Biochemistry
35:15494-15503
(1996)
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PubMed id:
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Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme.
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B.A.Fields,
F.A.Goldbaum,
W.Dall'Acqua,
E.L.Malchiodi,
A.Cauerhff,
F.P.Schwarz,
X.Ysern,
R.J.Poljak,
R.A.Mariuzza.
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ABSTRACT
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Using site-directed mutagenesis, X-ray crystallography, and titration
calorimetry, we have examined the structural and thermodynamic consequences of
removing specific hydrogen bonds in an antigen-antibody interface. Crystal
structures of three antibody FvD1.3 mutants, VLTyr50Ser (VLY50S), VHTyr32Ala
(VHY32A), and VHTyr101Phe (VHY101F), bound to hen egg white lysozyme (HEL) have
been determined at resolutions ranging from 1.85 to 2.10 A. In the wild-type
(WT) FvD1.3-HEL complex, the hydroxyl groups of VLTyr50, VHTyr32, and VHTyr101
each form at least one hydrogen bond with the lysozyme antigen. Thermodynamic
parameters for antibody-antigen association have been measured using isothermal
titration calorimetry, giving equilibrium binding constants Kb (M-1) of 2.6 x
10(7) (VLY50S), 7.0 x 10(7) (VHY32A), and 4.0 x 10(6) (VHY101F). For the WT
complex, Kb is 2.7 x 10(8) M-1; thus, the affinities of the mutant Fv fragments
for HEL are 10-, 4-, and 70-fold lower than that of the original antibody,
respectively. In all three cases entropy compensation results in an affinity
loss that would otherwise be larger. Comparison of the three mutant crystal
structures with the WT structure demonstrates that the removal of direct
antigen-antibody hydrogen bonds results in minimal shifts in the positions of
the remaining protein atoms. These observations show that this complex is
considerably tolerant, both structurally and thermodynamically, to the
truncation of antibody side chains that form hydrogen bonds with the antigen.
Alterations in interface solvent structure for two of the mutant complexes
(VLY50S and VHY32A) appear to compensate for the unfavorable enthalpy changes
when protein-protein interactions are removed. These changes in solvent
structure, along with the increased mobility of side chains near the mutation
site, probably contribute to the observed entropy compensation. For the VHY101F
complex, the nature of the large entropy compensation is not evident from a
structural comparison of the WT and mutant complexes. Differences in the local
structure and dynamics of the uncomplexed Fv molecules may account for the
entropic discrepancy in this case.
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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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A.Yokota,
K.Tsumoto,
M.Shiroishi,
T.Nakanishi,
H.Kondo,
and
I.Kumagai
(2010).
Contribution of asparagine residues to the stabilization of a proteinaceous antigen-antibody complex, HyHEL-10-hen egg white lysozyme.
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J Biol Chem,
285,
7686-7696.
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PDB codes:
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K.Tsumoto,
A.Yokota,
Y.Tanaka,
M.Ui,
T.Tsumuraya,
I.Fujii,
I.Kumagai,
Y.Nagumo,
H.Oguri,
M.Inoue,
and
M.Hirama
(2008).
Critical contribution of aromatic rings to specific recognition of polyether rings. The case of ciguatoxin CTX3C-ABC and its specific antibody 1C49.
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J Biol Chem,
283,
12259-12266.
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PDB code:
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M.Shiroishi,
K.Tsumoto,
Y.Tanaka,
A.Yokota,
T.Nakanishi,
H.Kondo,
and
I.Kumagai
(2007).
Structural consequences of mutations in interfacial Tyr residues of a protein antigen-antibody complex. The case of HyHEL-10-HEL.
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J Biol Chem,
282,
6783-6791.
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PDB codes:
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P.Monecke,
T.Borosch,
J.Brickmann,
and
S.M.Kast
(2006).
Determination of the interfacial water content in protein-protein complexes from free energy simulations.
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Biophys J,
90,
841-850.
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R.J.Duquesnoy
(2006).
A structurally based approach to determine HLA compatibility at the humoral immune level.
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Hum Immunol,
67,
847-862.
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R.L.Remmele,
W.J.Callahan,
S.Krishnan,
L.Zhou,
P.V.Bondarenko,
A.C.Nichols,
G.R.Kleemann,
G.D.Pipes,
S.Park,
S.Fodor,
E.Kras,
and
D.N.Brems
(2006).
Active dimer of Epratuzumab provides insight into the complex nature of an antibody aggregate.
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J Pharm Sci,
95,
126-145.
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F.Rodier,
R.P.Bahadur,
P.Chakrabarti,
and
J.Janin
(2005).
Hydration of protein-protein interfaces.
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Proteins,
60,
36-45.
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G.H.Cohen,
E.W.Silverton,
E.A.Padlan,
F.Dyda,
J.A.Wibbenmeyer,
R.C.Willson,
and
D.R.Davies
(2005).
Water molecules in the antibody-antigen interface of the structure of the Fab HyHEL-5-lysozyme complex at 1.7 A resolution: comparison with results from isothermal titration calorimetry.
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Acta Crystallogr D Biol Crystallogr,
61,
628-633.
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PDB code:
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N.Basdevant,
D.Borgis,
and
T.Ha-Duong
(2004).
A semi-implicit solvent model for the simulation of peptides and proteins.
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J Comput Chem,
25,
1015-1029.
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A.Yokota,
K.Tsumoto,
M.Shiroishi,
H.Kondo,
and
I.Kumagai
(2003).
The role of hydrogen bonding via interfacial water molecules in antigen-antibody complexation. The HyHEL-10-HEL interaction.
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J Biol Chem,
278,
5410-5418.
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PDB codes:
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L.O.Essen,
A.Harrenga,
C.Ostermeier,
and
H.Michel
(2003).
1.3 A X-ray structure of an antibody Fv fragment used for induced membrane-protein crystallization.
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Acta Crystallogr D Biol Crystallogr,
59,
677-687.
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PDB code:
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N.Sinha,
S.Mohan,
C.A.Lipschultz,
and
S.J.Smith-Gill
(2002).
Differences in electrostatic properties at antibody-antigen binding sites: implications for specificity and cross-reactivity.
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Biophys J,
83,
2946-2968.
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K.Burgess,
I.Han,
A.Zhang,
W.H.Zheng,
K.Shanmugam,
M.S.Featherstone,
and
H.U.Saragovi
(2001).
DiSSiMiL: Diverse Small Size Mini-Libraries applied to simple and rapid epitope mapping of a monoclonal antibody.
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J Pept Res,
57,
68-76.
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P.V.Afonin,
A.V.Fokin,
I.N.Tsygannik,
I.Y.Mikhailova,
L.V.Onoprienko,
I.I.Mikhaleva,
V.T.Ivanov,
T.Y.Mareeva,
V.A.Nesmeyanov,
N.Li,
W.A.Pangborn,
W.L.Duax,
and
V.Z.Pletnev
(2001).
Crystal structure of an anti-interleukin-2 monoclonal antibody Fab complexed with an antigenic nonapeptide.
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Protein Sci,
10,
1514-1521.
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PDB code:
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D.Fleury,
R.S.Daniels,
J.J.Skehel,
M.Knossow,
and
T.Bizebard
(2000).
Structural evidence for recognition of a single epitope by two distinct antibodies.
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Proteins,
40,
572-578.
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PDB code:
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E.J.Sundberg,
M.Urrutia,
B.C.Braden,
J.Isern,
D.Tsuchiya,
B.A.Fields,
E.L.Malchiodi,
J.Tormo,
F.P.Schwarz,
and
R.A.Mariuzza
(2000).
Estimation of the hydrophobic effect in an antigen-antibody protein-protein interface.
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Biochemistry,
39,
15375-15387.
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PDB codes:
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Y.Li,
H.Li,
S.J.Smith-Gill,
and
R.A.Mariuzza
(2000).
Three-dimensional structures of the free and antigen-bound Fab from monoclonal antilysozyme antibody HyHEL-63(,).
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Biochemistry,
39,
6296-6309.
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PDB codes:
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J.J.Boniface,
Z.Reich,
D.S.Lyons,
and
M.M.Davis
(1999).
Thermodynamics of T cell receptor binding to peptide-MHC: evidence for a general mechanism of molecular scanning.
|
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Proc Natl Acad Sci U S A,
96,
11446-11451.
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P.A.Ramsland,
B.F.Movafagh,
M.Reichlin,
and
A.B.Edmundson
(1999).
Interference of rheumatoid factor activity by aspartame, a dipeptide methyl ester.
|
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J Mol Recognit,
12,
249-257.
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B.C.Braden,
E.R.Goldman,
R.A.Mariuzza,
and
R.J.Poljak
(1998).
Anatomy of an antibody molecule: structure, kinetics, thermodynamics and mutational studies of the antilysozyme antibody D1.3.
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Immunol Rev,
163,
45-57.
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D.Fleury,
S.A.Wharton,
J.J.Skehel,
M.Knossow,
and
T.Bizebard
(1998).
Antigen distortion allows influenza virus to escape neutralization.
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Nat Struct Biol,
5,
119-123.
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PDB codes:
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W.Dall'Acqua,
A.L.Simon,
M.G.Mulkerrin,
and
P.Carter
(1998).
Contribution of domain interface residues to the stability of antibody CH3 domain homodimers.
|
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Biochemistry,
37,
9266-9273.
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W.Dall'Acqua,
E.R.Goldman,
W.Lin,
C.Teng,
D.Tsuchiya,
H.Li,
X.Ysern,
B.C.Braden,
Y.Li,
S.J.Smith-Gill,
and
R.A.Mariuzza
(1998).
A mutational analysis of binding interactions in an antigen-antibody protein-protein complex.
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Biochemistry,
37,
7981-7991.
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PDB code:
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I.A.Wilson,
and
K.C.Garcia
(1997).
T-cell receptor structure and TCR complexes.
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Curr Opin Struct Biol,
7,
839-848.
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K.A.Xavier,
K.A.Shick,
S.J.Smith-Gil,
and
R.C.Willson
(1997).
Involvement of water molecules in the association of monoclonal antibody HyHEL-5 with bobwhite quail lysozyme.
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Biophys J,
73,
2116-2125.
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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
