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PDBsum entry 1ha9
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Protease inhibitor
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PDB id
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1ha9
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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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Solution structure of the squash trypsin inhibitor mcoti-Ii. A new family for cyclic knottins.
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Authors
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A.Heitz,
J.F.Hernandez,
J.Gagnon,
T.T.Hong,
T.T.Pham,
T.M.Nguyen,
D.Le-Nguyen,
L.Chiche.
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Ref.
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Biochemistry, 2001,
40,
7973-7983.
[DOI no: ]
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PubMed id
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Abstract
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The "knottin" fold is a stable cysteine-rich scaffold, in which one disulfide
crosses the macrocycle made by two other disulfides and the connecting backbone
segments. This scaffold is found in several protein families with no
evolutionary relationships. In the past few years, several homologous peptides
from the Rubiaceae and Violaceae families were shown to define a new structural
family based on macrocyclic knottin fold. We recently isolated from Momordica
cochinchinensis seeds the first known macrocyclic squash trypsin inhibitors.
These compounds are the first members of a new family of cyclic knottins. In
this paper, we present NMR structural studies of one of them, MCoTI-II, and of a
beta-Asp rearranged form, MCoTI-IIb. Both compounds display similar and
well-defined conformations. These cyclic squash inhibitors share a similar
conformation with noncyclic squash inhibitors such as CPTI-II, and it is
postulated that the main effect of the cyclization is a reduced sensitivity to
exo-proteases. On the contrary, clear differences were detected with the
three-dimensional structures of other known cyclic knottins, i.e., kalata B1 or
circulin A. The two-disulfide cystine-stabilized beta-sheet motif [Heitz et al.
(1999) Biochemistry 38, 10615-10625] is conserved in the two families, whereas
in the C-to-N linker, one disulfide bridge and one loop are differently located.
The molecular surface of MCoTI-II is almost entirely charged in contrast to
circulin A that displays a well-marked amphiphilic character. These differences
might explain why the isolated macrocyclic squash inhibitors from M.
cochinchinensis display no significant antibacterial activity, whereas circulins
and kalata B1 do.
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