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PDBsum entry 3c05
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Blood clotting/antitumor protein
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PDB id
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3c05
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References listed in PDB file
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Key reference
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Title
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Structure of acostatin, A dimeric disintegrin from southern copperhead (agkistrodon contortrix contortrix), At 1.7 a resolution.
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Authors
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N.Moiseeva,
R.Bau,
S.D.Swenson,
F.S.Markland,
J.Y.Choe,
Z.J.Liu,
M.Allaire.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2008,
64,
466-470.
[DOI no: ]
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PubMed id
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Abstract
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Disintegrins are a family of small (4-14 kDa) proteins that bind to another
class of proteins, integrins. Therefore, as integrin inhibitors, they can be
exploited as anticancer and antiplatelet agents. Acostatin, an alphabeta
heterodimeric disintegrin, has been isolated from the venom of Southern
copperhead (Agkistrodon contortrix contortrix). The three-dimensional structure
of acostatin has been determined by macromolecular crystallography using the
molecular-replacement method. The asymmetric unit of the acostatin crystals
consists of two heterodimers. The structure has been refined to an R(work) and
R(free) of 18.6% and 21.5%, respectively, using all data in the 20-1.7 A
resolution range. The structure of all subunits is similar and is well ordered
into N-terminal and C-terminal clusters with four intramolecular disulfide
bonds. The overall fold consists of short beta-sheets, each of which is formed
by a pair of antiparallel beta-strands connected by beta-turns and flexible
loops of different lengths. Conformational flexibility is found in the RGD loops
and in the C-terminal segment. The interaction of two N-terminal clusters via
two intermolecular disulfide bridges anchors the alphabeta chains of the
acostatin dimers. The C-terminal clusters of the heterodimer project in opposite
directions and form a larger angle between them in comparison with other dimeric
disintegrins. Extensive interactions are observed between two heterodimers,
revealing an alphabetabetaalpha acostatin tetramer. Further experiments are
required to identify whether the alphabetabetaalpha acostatin complex plays a
functional role in vivo.
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Figure 1.
Figure 1 Electron-density fit of the model showing (a) observed
differences in the amino-acid sequence of the  -
and  -chains
of acostatin represented by subunits A and B, respectively, (b)
all Cys13 residues identified as rotamer outliers and (c) the
carboxyl group of the C-terminal residue Phe63 of subunit A.
This figure was prepared using PyMOL (DeLano, 2002[DeLano, W. L.
(2002). The PyMOL Molecular Graphics System. DeLano Scientific,
San Carlos, California, USA. http://www.pymol.org .]).
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Figure 3.
Figure 3 Sequence alignment of acostatin with trimestatin,
schistatin and the E. carinatus heterodimer.
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The above figures are
reprinted
from an Open Access publication published by the IUCr:
Acta Crystallogr D Biol Crystallogr
(2008,
64,
466-470)
copyright 2008.
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