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PDBsum entry 1a2a
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Presynaptic neurotoxin
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PDB id
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1a2a
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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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Crystal structure of agkistrodotoxin, A phospholipase a2-Type presynaptic neurotoxin from agkistrodon halys pallas.
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Authors
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L.Tang,
Y.C.Zhou,
Z.J.Lin.
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Ref.
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J Mol Biol, 1998,
282,
1.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of agkistrodotoxin containing eight copies of molecules in
the asymmetric unit has been determined at 2.8 A resolution to a
crystallographic R factor of 0.207 by the molecular replacement technique. Two
spatially adjacent regions of agkistrodotoxin molecule, turn 55-61 and stretch
85-91, are remarkably different from those of non-neurotoxic isoforms in
conformation and electrostatic characteristics. These regions are likely to be
involved in the recognition of agkistrodotoxin towards the specific receptor at
the presynaptic membrane. The structural comparison of the interfacial
recognition site with non-neurotoxic isoforms reveals a decreased hydrophobicity
and lack of residues with bulky hydrophobic side-chains (i.e. Trp) to serve as
membrane anchors. This structural feature of agkistrodotoxin may be related to
the reduced non-specific binding of the toxin to non-targeted membrane before it
arrives at the presynaptic membrane and recognizes the putative receptor. A
unique hydrophobic patch including residues I19, P20, F21, A23, F24, M118 and
F119 is found on the surface of the molecule near the entrance of the
hydrophobic channel which plays an important role in crystal packing. The
interaction mode between the patches might give a clue to the binding of the
neurotoxin on the membrane. The agkistrodotoxin molecules in the asymmetric unit
form two tetramers and each tetramer exhibits a novel "dimer of
dimers"-like structure. A molecule-spanning four-stranded antiparallel
beta-sheet is formed by the beta-wings of two molecules within a tetramer.
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Figure 2.
Figure 2. (a) Stereo view of the local structure of turn
55-61 and stretch 85-91. H-bonds are shown as broken lines. (b)
2F[o] -F[c] electron density map contoured at 1.3s of the
proposed neurotoxic site.
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Figure 3.
Figure 3. Stereo view of contacted hydrophobic patches from
molecule A of a tetramer (thick line) and molecule D of a
neighboring tetramer (thin line). The side-chains of residues
I19, P20, F21, A23, F24, M118 and F119 are shown.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
282,
1-0)
copyright 1998.
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Secondary reference #1
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Title
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Crystal structure of agkistrodotoxin, A phospholipase a2-Type presynaptic neurotoxin from agkistrodon halys pallas.
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Authors
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L.Tang,
Y.C.Zhou,
Z.J.Lin.
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Ref.
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J Mol Biol, 1998,
282,
1.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. (a) Stereo view of the local structure of turn
55-61 and stretch 85-91. H-bonds are shown as broken lines. (b)
2F[o] -F[c] electron density map contoured at 1.3s of the
proposed neurotoxic site.
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Figure 3.
Figure 3. Stereo view of contacted hydrophobic patches from
molecule A of a tetramer (thick line) and molecule D of a
neighboring tetramer (thin line). The side-chains of residues
I19, P20, F21, A23, F24, M118 and F119 are shown.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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