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* Residue conservation analysis
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DOI no:
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Proc Natl Acad Sci U S A
89:7154-7158
(1992)
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PubMed id:
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Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type 1.
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X.M.He,
F.Rüker,
E.Casale,
D.C.Carter.
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ABSTRACT
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The three-dimensional structure of a human monoclonal antibody (Fab), which
binds specifically to a major epitope of the transmembrane protein gp41 of the
human immunodeficiency virus type 1, has been determined by crystallographic
methods to a resolution of 2.7 A. It has been previously determined that this
antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1
(kappa), and exhibits antibody-dependent cellular cytotoxicity. The quaternary
structure of the Fab is in an extended conformation with an elbow bend angle
between the constant and variable domains of 175 degrees. Structurally, four of
the hypervariable loops can be classified according to previously recognized
canonical structures. The third hypervariable loops of the heavy (H3) and light
chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H,
is unusually extended from the surface. The complementarity-determining region
forms a hydrophobic binding pocket that is created primarily from hypervariable
loops L3, H3, and H2.
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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.S.McLellan,
M.Pancera,
C.Carrico,
J.Gorman,
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R.Khayat,
R.Louder,
R.Pejchal,
M.Sastry,
K.Dai,
S.O'Dell,
N.Patel,
S.Shahzad-ul-Hussan,
Y.Yang,
B.Zhang,
T.Zhou,
J.Zhu,
J.C.Boyington,
G.Y.Chuang,
D.Diwanji,
I.Georgiev,
Y.D.Kwon,
D.Lee,
M.K.Louder,
S.Moquin,
S.D.Schmidt,
Z.Y.Yang,
M.Bonsignori,
J.A.Crump,
S.H.Kapiga,
N.E.Sam,
B.F.Haynes,
D.R.Burton,
W.C.Koff,
L.M.Walker,
S.Phogat,
R.Wyatt,
J.Orwenyo,
L.X.Wang,
J.Arthos,
C.A.Bewley,
J.R.Mascola,
G.J.Nabel,
W.R.Schief,
A.B.Ward,
I.A.Wilson,
and
P.D.Kwong
(2011).
Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.
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Nature,
480,
336-343.
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PDB codes:
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D.Kuroda,
H.Shirai,
M.Kobori,
and
H.Nakamura
(2009).
Systematic classification of CDR-L3 in antibodies: implications of the light chain subtypes and the VL-VH interface.
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Proteins,
75,
139-146.
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M.Niemi,
J.Jänis,
S.Jylhä,
J.M.Kallio,
N.Hakulinen,
M.L.Laukkanen,
K.Takkinen,
and
J.Rouvinen
(2008).
Characterization and crystallization of a recombinant IgE Fab fragment in complex with the bovine beta-lactoglobulin allergen.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
25-28.
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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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L.del Pozo Yauner,
E.Ortiz,
and
B.Becerril
(2006).
The CDR1 of the human lambdaVI light chains adopts a new canonical structure.
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Proteins,
62,
122-129.
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M.Jacquemin,
C.M.Radcliffe,
R.Lavend'homme,
M.R.Wormald,
L.Vanderelst,
G.Wallays,
J.Dewaele,
D.Collen,
J.Vermylen,
R.A.Dwek,
J.M.Saint-Remy,
P.M.Rudd,
and
M.Dewerchin
(2006).
Variable region heavy chain glycosylation determines the anticoagulant activity of a factor VIII antibody.
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J Thromb Haemost,
4,
1047-1055.
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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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F.J.Stevens
(2004).
Hypothetical structure of human serum amyloid A protein.
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Amyloid,
11,
71-80.
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D.Altschuh
(2002).
Cyclosporin A as a model antigen: immunochemical and structural studies.
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J Mol Recognit,
15,
277-285.
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E.Vargas-Madrazo,
and
E.Paz-García
(2002).
Modifications to canonical structure sequence patterns: analysis for L1 and L3.
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Proteins,
47,
250-254.
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P.A.Ramsland,
and
W.Farrugia
(2002).
Crystal structures of human antibodies: a detailed and unfinished tapestry of immunoglobulin gene products.
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J Mol Recognit,
15,
248-259.
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J.L.Torán,
L.Sánchez-Pulido,
L.Kremer,
G.del Real,
A.Valencia,
and
C.Martínez-A
(2001).
Improvement in affinity and HIV-1 neutralization by somatic mutation in the heavy chain first complementarity-determining region of antibodies triggered by HIV-1 infection.
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Eur J Immunol,
31,
128-137.
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P.Zhu,
W.C.Olson,
and
K.H.Roux
(2001).
Structural flexibility and functional valence of CD4-IgG2 (PRO 542): potential for cross-linking human immunodeficiency virus type 1 envelope spikes.
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J Virol,
75,
6682-6686.
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F.J.Stevens
(2000).
Four structural risk factors identify most fibril-forming kappa light chains.
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Amyloid,
7,
200-211.
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J.Yi,
and
A.M.Skalka
(2000).
Mapping epitopes of monoclonal antibodies against HIV-1 integrase with limited proteolysis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
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Biopolymers,
55,
308-318.
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L.Choulier,
V.Lafont,
N.Hugo,
and
D.Altschuh
(2000).
Covariance analysis of protein families: the case of the variable domains of antibodies.
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Proteins,
41,
475-484.
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R.Stanfield,
E.Cabezas,
A.Satterthwait,
E.Stura,
A.Profy,
and
I.Wilson
(1999).
Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs.
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Structure,
7,
131-142.
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PDB codes:
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R.Vidal,
F.Goñi,
F.Stevens,
P.Aucouturier,
A.Kumar,
B.Frangione,
J.Ghiso,
and
G.Gallo
(1999).
Somatic mutations of the L12a gene in V-kappa(1) light chain deposition disease: potential effects on aberrant protein conformation and deposition.
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Am J Pathol,
155,
2009-2017.
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Z.C.Fan,
L.Shan,
B.Z.Goldsteen,
L.W.Guddat,
A.Thakur,
N.F.Landolfi,
M.S.Co,
M.Vasquez,
C.Queen,
P.A.Ramsland,
and
A.B.Edmundson
(1999).
Comparison of the three-dimensional structures of a humanized and a chimeric Fab of an anti-gamma-interferon antibody.
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J Mol Recognit,
12,
19-32.
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PDB codes:
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J.B.Charbonnier,
B.Golinelli-Pimpaneau,
B.Gigant,
D.S.Tawfik,
R.Chap,
D.G.Schindler,
S.H.Kim,
B.S.Green,
Z.Eshhar,
and
M.Knossow
(1997).
Structural convergence in the active sites of a family of catalytic antibodies.
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Science,
275,
1140-1142.
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PDB codes:
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R.R.Joshi
(1996).
A self-organizing cognitive network of antibody repertoire development.
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J Comput Biol,
3,
529-545.
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H.Lilie,
R.Jaenicke,
and
J.Buchner
(1995).
Characterization of a quaternary-structured folding intermediate of an antibody Fab-fragment.
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Protein Sci,
4,
917-924.
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I.M.Tomlinson,
J.P.Cox,
E.Gherardi,
A.M.Lesk,
and
C.Chothia
(1995).
The structural repertoire of the human V kappa domain.
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EMBO J,
14,
4628-4638.
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K.D.Janda,
C.H.Lo,
T.Li,
C.F.Barbas,
P.Wirsching,
and
R.A.Lerner
(1994).
Direct selection for a catalytic mechanism from combinatorial antibody libraries.
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Proc Natl Acad Sci U S A,
91,
2532-2536.
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H.Lilie,
K.Lang,
R.Rudolph,
and
J.Buchner
(1993).
Prolyl isomerases catalyze antibody folding in vitro.
|
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Protein Sci,
2,
1490-1496.
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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
