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PDBsum entry 1mf2
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Immunoglobulin
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PDB id
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1mf2
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure of an FAB-Peptide complex: structural basis of HIV-1 protease inhibition by a monoclonal antibody.
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Authors
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J.Lescar,
R.Stouracova,
M.M.Riottot,
V.Chitarra,
J.Brynda,
M.Fabry,
M.Horejsi,
J.Sedlacek,
G.A.Bentley.
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Ref.
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J Mol Biol, 1997,
267,
1207-1222.
[DOI no: ]
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PubMed id
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Abstract
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F11.2.32, a monoclonal antibody raised against HIV-1 protease (Kd = 5 nM), which
inhibits proteolytic activity of the enzyme (K(inh) = 35(+/-3)nM), has been
studied by crystallographic methods. The three-dimensional structure of the
complex between the Fab fragment and a synthetic peptide, spanning residues 36
to 46 of the protease, has been determined at 2.2 A resolution, and that of the
Fab in the free state has been determined at 2.6 A resolution. The refined model
of the complex reveals ten well-ordered residues of the peptide (P36 to P45)
bound in a hydrophobic cavity at the centre of the antigen-binding site. The
peptide adopts a beta hairpin-like structure in which residues P38 to P42 form a
type II beta-turn conformation. An intermolecular antiparallel beta-sheet is
formed between the peptide and the CDR3-H loop of the antibody; additional polar
interactions occur between main-chain atoms of the peptide and hydroxyl groups
from tyrosine residues protruding from CDR1-L and CDR3-H. Three water molecules,
located at the antigen-antibody interface, mediate polar interactions between
the peptide and the most buried hypervariable loops, CDR3-L and CDR1-H. A
comparison between the free and complexed Fab fragments shows that significant
conformational changes occur in the long hypervariable regions, CDR1-L and
CDR3-H, upon binding the peptide. The conformation of the bound peptide, which
shows no overall structural similarity to the corresponding segment in HIV-1
protease, suggests that F11.2.32 might inhibit proteolysis by distorting the
native structure of the enzyme.
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Figure 5.
Figure 5. View of the interaction between the peptide
and the molecular surface of the antigen-binding site,
colour coded for electrostatic potential: red for negative
and blue for positive; prepared with program GRASP
(Nicholls et al., 1991).
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Figure 7.
Figure 7. Comparison between the structure adopted by peptide(P36-P46) in the complex with Fab F11.2.32 and the
conformation adopted by this segment in the native protease (PDB entry code 3hvp). (a) A schematic view of the pro-
tease in which the location of the epitope recognised by F11.2.32 is shown in red. (b) Ramachandran graph indicating
the differences in f-j angles of the segment 36 to 46 in the bound peptide (black) and the protease (red); residues are
named at the positions for the bound peptide and broken lines connect equivalent residues of the peptide and the
protease. Comparison of residues 36 to 45 of the protease (red) and bound peptide (yellow): (c) after superimposing
residues 36 to 40 and (d) after superimposing residues 41 to 44. The Figure was prepared with program MOLSCRIPT
(Kraulis, 1991).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1997,
267,
1207-1222)
copyright 1997.
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Secondary reference #1
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Title
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Preliminary crystallographic studies of an anti-Hiv-1 protease antibody that inhibits enzyme activity.
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Authors
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J.Lescar,
R.Stouracova,
M.M.Riottot,
V.Chitarra,
J.Brynda,
M.Fabry,
M.Horejsi,
J.Sedlacek,
G.A.Bentley.
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Ref.
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Protein Sci, 1996,
5,
966-968.
[DOI no: ]
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PubMed id
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The above figure is
reproduced from the cited reference
with permission from the Protein Society
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