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* Residue conservation analysis
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Enzyme class:
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Chains L, H:
E.C.3.4.21.5
- thrombin.
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Reaction:
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Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.
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DOI no:
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Acta Crystallogr D Biol Crystallogr
52:272-282
(1996)
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PubMed id:
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An ambiguous structure of a DNA 15-mer thrombin complex.
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K.Padmanabhan,
A.Tulinsky.
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ABSTRACT
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The structure of a complex between thrombin and a GGTTGGTGTGGTTGG DNA 15-mer has
been analyzed crystallographically. The solution NMR structure of the 15-mer has
two stacked G-quartets similar to that found in the previous X-ray structure
determination of the 15-mer-thrombin complex [Padmanabhan, Padmanabhan, Ferrara,
Sadler & Tulinsky (1993). J. Biol. Chem. 268, 17651-17654]; the strand
polarity, however, is reversed from that of the crystallographic structure. The
structure of the complex here has been redetermined with better diffraction data
confirming the previous crystallographic structure but also indicating that the
NMR solution structure fits equally well. Both 15-mer complex structures refined
to an R value of about 0.16 presenting a disconcerting ambiguity. Since the two
15-mer structures associate with thrombin in different ways (through the TGT
loop in the X-ray and TT loop in the NMR model), other independent lines of
physical or chemical evidence are required to resolve the ambiguity.
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Selected figure(s)
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Figure 1.
Fig. 1. Schematic drawings of the X-ray (left) and NMR (right)
structures of the aptamer. "IT loops span wide grooves, TGT spans
narrow groove in X-ray structure and
vice versa
in NMR structure.
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Figure 7.
Fig. 7. Stereoview of the hydrophobic
interaction sites of T3 and TI2 of
the NMR model of the aptamer.
The DNA is shown in thin lines
and thrombin residues, which form
the hydrophobic pockets located in
the fibrinogen exosite at top (in
bold). Heparin binding-site inter-
actions at bottom (primed resi-
dues). Only bases with good
density shown.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(1996,
52,
272-282)
copyright 1996.
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Figures were
selected
by an automated process.
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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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M.A.Ochsenkühn,
and
C.J.Campbell
(2010).
Probing biomolecular interactions using surface enhanced Raman spectroscopy: label-free protein detection using a G-quadruplex DNA aptamer.
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Chem Commun (Camb),
46,
2799-2801.
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T.J.Povsic,
B.A.Sullenger,
S.L.Zelenkofske,
C.P.Rusconi,
and
R.C.Becker
(2010).
Translating nucleic Acid aptamers to antithrombotic drugs in cardiovascular medicine.
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J Cardiovasc Transl Res,
3,
704-716.
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R.H.Huang,
D.H.Fremont,
J.L.Diener,
R.G.Schaub,
and
J.E.Sadler
(2009).
A structural explanation for the antithrombotic activity of ARC1172, a DNA aptamer that binds von Willebrand factor domain A1.
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Structure,
17,
1476-1484.
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PDB codes:
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S.M.Nimjee,
S.Oney,
Z.Volovyk,
K.M.Bompiani,
S.B.Long,
M.Hoffman,
and
B.A.Sullenger
(2009).
Synergistic effect of aptamers that inhibit exosites 1 and 2 on thrombin.
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RNA,
15,
2105-2111.
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B.Pagano,
L.Martino,
A.Randazzo,
and
C.Giancola
(2008).
Stability and binding properties of a modified thrombin binding aptamer.
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Biophys J,
94,
562-569.
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S.B.Long,
M.B.Long,
R.R.White,
and
B.A.Sullenger
(2008).
Crystal structure of an RNA aptamer bound to thrombin.
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RNA,
14,
2504-2512.
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PDB code:
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S.Balamurugan,
A.Obubuafo,
S.A.Soper,
and
D.A.Spivak
(2008).
Surface immobilization methods for aptamer diagnostic applications.
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Anal Bioanal Chem,
390,
1009-1021.
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C.G.Peng,
and
M.J.Damha
(2007).
G-quadruplex induced stabilization by 2'-deoxy-2'-fluoro-D-arabinonucleic acids (2'F-ANA).
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Nucleic Acids Res,
35,
4977-4988.
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C.Lin,
E.Katilius,
Y.Liu,
J.Zhang,
and
H.Yan
(2006).
Self-assembled signaling aptamer DNA arrays for protein detection.
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Angew Chem Int Ed Engl,
45,
5296-5301.
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J.Li,
J.J.Correia,
L.Wang,
J.O.Trent,
and
J.B.Chaires
(2005).
Not so crystal clear: the structure of the human telomere G-quadruplex in solution differs from that present in a crystal.
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Nucleic Acids Res,
33,
4649-4659.
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N.A.Raffler,
J.Schneider-Mergener,
and
M.Famulok
(2003).
A novel class of small functional peptides that bind and inhibit human alpha-thrombin isolated by mRNA display.
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Chem Biol,
10,
69-79.
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V.Dapić,
V.Abdomerović,
R.Marrington,
J.Peberdy,
A.Rodger,
J.O.Trent,
and
P.J.Bates
(2003).
Biophysical and biological properties of quadruplex oligodeoxyribonucleotides.
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Nucleic Acids Res,
31,
2097-2107.
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J.Sühnel
(2001).
Beyond nucleic acid base pairs: from triads to heptads.
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Biopolymers,
61,
32-51.
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R.H.Shafer,
and
I.Smirnov
(2000).
Biological aspects of DNA/RNA quadruplexes.
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Biopolymers,
56,
209-227.
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G.D.Strahan,
M.A.Keniry,
and
R.H.Shafer
(1998).
NMR structure refinement and dynamics of the K+-[d(G3T4G3)]2 quadruplex via particle mesh Ewald molecular dynamics simulations.
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Biophys J,
75,
968-981.
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J.Feigon,
T.Dieckmann,
and
F.W.Smith
(1996).
Aptamer structures from A to zeta.
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Chem Biol,
3,
611-617.
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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
