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PDBsum entry 2rdk
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Antiviral protein
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PDB id
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2rdk
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References listed in PDB file
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Key reference
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Title
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Conformational gating of dimannose binding to the antiviral protein cyanovirin revealed from the crystal structure at 1.35 a resolution.
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Authors
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R.Fromme,
Z.Katiliene,
P.Fromme,
G.Ghirlanda.
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Ref.
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Protein Sci, 2008,
17,
939-944.
[DOI no: ]
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PubMed id
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Abstract
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Cyanovirin (CV-N) is a small lectin with potent HIV neutralization activity,
which could be exploited for a mucosal defense against HIV infection. The
wild-type (wt) protein binds with high affinity to mannose-rich oligosaccharides
on the surface of gp120 through two quasi-symmetric sites, located in domains A
and B. We recently reported on a mutant of CV-N that contained a single
functional mannose-binding site, domain B, showing that multivalent binding to
oligomannosides is necessary for antiviral activity. The structure of the
complex with dimannose determined at 1.8 A resolution revealed a different
conformation of the binding site than previously observed in the NMR structure
of wt CV-N. Here, we present the 1.35 A resolution structure of the complex,
which traps three different binding conformations of the site and provides
experimental support for a locking and gating mechanism in the nanoscale time
regime observed by molecular dynamics simulations.
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Figure 1.
Crystal structure of P51G-m4-CVN at 1.35 A resolution:
cartoon representation of one monomer in complex with dimannose.
Domain A (green) contains four mutations (K3N, T7A, E23I, N93A,
highlighted as red sticks) in the binding site, resulting in
loss of binding (Chang and Bewley 2002). Domain B (blue) is
unaltered and binds to dimannose. A P51G mutation in the hinge
region stabilizes the monomer (Barrientos et al. 2002). The
sequence of P51G-m4-CVN is reported below; domains A and B are
represented in green and blue, respectively, while mutations
from wt are in red. Figure generated with PyMOL (DeLano
Scientific; http://www.pymol.org).
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Figure 2.
Overlay of the backbone hinge region (residues 46 --57) of
cyanovirin, monomer and dimer, and of P51G-m4-CVN. The monomeric
NMR structure of wt CV-N (PDB code 2EZM) is represented in
yellow, while the domain-swapped crystal structure (PDB code
1M5M) is represented in gray, and the monomeric crystal
structure of P51G-m4-CVN in green (PDB code 2RDK; this work).
Only the side chain of P51 (wt) is shown. In 2EZM, S52 assumes
disallowed backbone dihedral angles.
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The above figures are
reprinted
from an Open Access publication published by the Protein Society:
Protein Sci
(2008,
17,
939-944)
copyright 2008.
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Secondary reference #1
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Title
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A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity.
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Authors
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R.Fromme,
Z.Katiliene,
B.Giomarelli,
F.Bogani,
J.Mc mahon,
T.Mori,
P.Fromme,
G.Ghirlanda.
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Ref.
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Biochemistry, 2007,
46,
9199-9207.
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PubMed id
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