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* Residue conservation analysis
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Proteins
29:161-171
(1997)
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PubMed id:
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VL:VH domain rotations in engineered antibodies: crystal structures of the Fab fragments from two murine antitumor antibodies and their engineered human constructs.
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M.J.Banfield,
D.J.King,
A.Mountain,
R.L.Brady.
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ABSTRACT
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The crystal structures of two pairs of Fab fragments have been determined. The
pairs comprise both a murine and an engineered human form, each derived from the
antitumor antibodies A5B7 and CTM01. Although antigen specificity is maintained
within the pairs, antigen affinity varies. A comparison of the hypervariable
loops for each pair of antibodies shows their structure has been well maintained
in grafting, supporting the canonical loop model. Detailed structural analysis
of the binding sites and domain arrangements for these antibodies suggests the
differences in antigen affinity observed are likely to be due to inherent
flexibility of the hypervariable loops and movements at the VL:VH domain
interface. The four structures provide the first opportunity to study in detail
the effects of protein engineering on specific antibodies.
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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.Sivasubramanian,
A.Sircar,
S.Chaudhury,
and
J.J.Gray
(2009).
Toward high-resolution homology modeling of antibody Fv regions and application to antibody-antigen docking.
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Proteins,
74,
497-514.
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J.Du,
H.Wang,
C.Zhong,
B.Peng,
M.Zhang,
B.Li,
S.Huo,
Y.Guo,
and
J.Ding
(2007).
Structural basis for recognition of CD20 by therapeutic antibody Rituximab.
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J Biol Chem,
282,
15073-15080.
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PDB code:
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S.Li,
K.R.Schmitz,
P.D.Jeffrey,
J.J.Wiltzius,
P.Kussie,
and
K.M.Ferguson
(2005).
Structural basis for inhibition of the epidermal growth factor receptor by cetuximab.
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Cancer Cell,
7,
301-311.
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PDB codes:
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E.Carredano,
H.Baumann,
A.Grönberg,
N.Norrman,
G.Glad,
J.Zou,
O.Ersoy,
E.Steensma,
and
A.Axén
(2004).
A novel and conserved pocket of human kappa-Fab fragments: design, synthesis, and verification of directed affinity ligands.
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Protein Sci,
13,
1476-1488.
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R.Varghese,
Y.Mikyas,
P.L.Stewart,
and
R.Ralston
(2004).
Postentry neutralization of adenovirus type 5 by an antihexon antibody.
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J Virol,
78,
12320-12332.
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E.Vargas-Madrazo,
and
E.Paz-García
(2003).
An improved model of association for VH-VL immunoglobulin domains: asymmetries between VH and VL in the packing of some interface residues.
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J Mol Recognit,
16,
113-120.
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H.S.Cho,
K.Mason,
K.X.Ramyar,
A.M.Stanley,
S.B.Gabelli,
D.W.Denney,
and
D.J.Leahy
(2003).
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab.
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Nature,
421,
756-760.
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PDB codes:
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H.Haruyama,
S.Ito,
K.Miyadai,
T.Takahashi,
R.Kawaida,
T.Takayama,
H.Hanzawa,
T.Hata,
J.Yamaguchi,
H.Yoshida-Kato,
K.Ichikawa,
J.Ohsumi,
S.Yonehara,
and
N.Serizawa
(2002).
Humanization of the mouse anti-Fas antibody HFE7A and crystal structure of the humanized HFE7A Fab fragment.
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Biol Pharm Bull,
25,
1537-1545.
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PDB code:
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M.B.Berry,
K.A.Johnson,
W.Radding,
M.Fung,
R.Liou,
and
G.N.Phillips
(2001).
Structure of an anti-HIV monoclonal Fab antibody fragment specific to a gp120 C-4 region peptide.
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Proteins,
45,
281-282.
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PDB code:
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J.Maynard,
and
G.Georgiou
(2000).
Antibody engineering.
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Annu Rev Biomed Eng,
2,
339-376.
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B.Carrasco,
J.G.de la Torre,
O.Byron,
D.King,
C.Walters,
S.Jones,
and
S.E.Harding
(1999).
Novel size-independent modeling of the dilute solution conformation of the immunoglobulin IgG Fab' domain using SOLPRO and ELLIPS.
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Biophys J,
77,
2902-2910.
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J.Wally,
G.Kica,
Y.Zhang,
T.Ericsson,
L.H.Connors,
M.D.Benson,
J.J.Liepnieks,
J.Murray,
M.Skinner,
and
R.L.Comenzo
(1999).
Identification of a novel substitution in the constant region of a gene coding for an amyloidogenic kappa1 light chain.
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Biochim Biophys Acta,
1454,
49-56.
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S.Odani,
Y.Komori,
and
F.Gejyo
(1999).
Structural analysis of the amyloidogenic kappa Bence Jones protein (FUR).
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Amyloid,
6,
77-88.
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B.D.Zelus,
D.R.Wessner,
R.K.Williams,
M.N.Pensiero,
F.T.Phibbs,
M.deSouza,
G.S.Dveksler,
and
K.V.Holmes
(1998).
Purified, soluble recombinant mouse hepatitis virus receptor, Bgp1(b), and Bgp2 murine coronavirus receptors differ in mouse hepatitis virus binding and neutralizing activities.
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J Virol,
72,
7237-7244.
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P.J.Hudson
(1998).
Recombinant antibody fragments.
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Curr Opin Biotechnol,
9,
395-402.
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W.Dall'Acqua,
and
P.Carter
(1998).
Antibody engineering.
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Curr Opin Struct Biol,
8,
443-450.
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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
