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PDBsum entry 1imt
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References listed in PDB file
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Key reference
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Title
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A structural homologue of colipase in black mamba venom revealed by nmr floating disulphide bridge analysis.
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Authors
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J.Boisbouvier,
J.P.Albrand,
M.Blackledge,
M.Jaquinod,
H.Schweitz,
M.Lazdunski,
D.Marion.
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Ref.
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J Mol Biol, 1998,
283,
205-219.
[DOI no: ]
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PubMed id
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Abstract
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The solution structure of mamba intestinal toxin 1 (MIT1), isolated from
Dendroaspis polylepis polylepis venom, has been determined. This molecule is a
cysteine-rich polypeptide exhibiting no recognised family membership. Resistance
to MIT1 to classical specific endoproteases produced contradictory NMR and
biochemical information concerning disulphide-bridge topology. We have used
distance restraints allowing ambiguous partners between S atoms in combination
with NMR-derived structural information, to correctly determine the
disulphide-bridge topology. The resultant solution structure of MIT1, determined
to a resolution of 0.5 A, reveals an unexpectedly similar global fold with
respect to colipase, a protein involved in fatty acid digestion. Colipase
exhibits an analogous resistance to endoprotease activity, indicating for the
first time the possible topological origins of this biochemical property. The
biochemical and structural homology permitted us to propose a mechanically
related digestive function for MIT1 and provides novel information concerning
snake venom protein evolution.
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Figure 5.
Figure 5. Solution structure of MIT1. (a) Backbone and
disulphide-bridge heavy atoms from residues 5 to 80 of the 39
NMR conformers (calculations rMD, Table 1). N, C and C^a atoms
from residues 6 to 79 of each structure were superimposed on the
average structure atoms. Central core residue backbone atoms (5
to 10, 16 to 21, 29 to 43, 57 to 69 and 75 to 80) are displayed
in blue, extremity residue backbone atoms of each finger (11 to
15, 22 to 28, 44 to 56 and 70 to 74) are displayed in red, and
disulphide-bridges in yellow. (b) Stereo view of the conformer
closest to the mean structure of the 39 conformers shown in (a).
The following colours were used for the side-chains: blue, Arg
and Lys; red, Glu and Asp; yellow, Ala, Cys, Ile, Leu, Met, Phe,
Pro, Trp and Val; grey, Asn, Gln, Ser, Thr and His. Buried
side-chains of the inner ionic bridge; Asp10 and Arg54 are
displayed with a thicker stick and are labelled. The His46 O
atom is labelled.
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Figure 9.
Figure 9. Electrostatic potentials map of colipase and
MIT1. (a) and (b) The exposed surface of colipase, (c) and (d)
were coloured with the electrostatic potential [Gilson et al
1987] by linear interpolation between red (f(r)< -3 kT,
negative), white (f(r = 0 kT, neutral) and blue (f(r)>3 kT,
positive). (a) and (c) Surfaces were displayed with the same
orientation as Figure 5. (b) and (d) Representations were turned
by 180° with respect to the vertical axis.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
283,
205-219)
copyright 1998.
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