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PDBsum entry 1dg0
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References listed in PDB file
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Key reference
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Title
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Structures of the contryphan family of cyclic peptides. Role of electrostatic interactions in cis-Trans isomerism.
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Authors
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P.K.Pallaghy,
W.He,
E.C.Jimenez,
B.M.Olivera,
R.S.Norton.
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Ref.
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Biochemistry, 2000,
39,
12845-12852.
[DOI no: ]
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PubMed id
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Abstract
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The contryphan family of cyclic peptides, isolated recently from various species
of cone shell, has the conserved sequence motif NH(3)(+)-X(1)COD-WX(5)PWC-NH(2),
where X(1) is either Gly or absent, O is 4-trans-hydroxyproline, and X(5) is
Glu, Asp, or Gln. The solution structures described herein of two new naturally
occurring contryphan sequences, contryphan-Sm and des[Gly1]-contryphan-R, are
similar to those of contryphan-R, the structure of which has been determined
recently [Pallaghy et al. (1999) Biochemistry 38, 11553-11559]. The (1)H NMR
chemical shifts of another naturally occurring peptide, contryphan-P, indicate
that it also adopts a similar structure. All of these contryphans exist in
solution as a mixture of two conformers due to cis-trans isomerization about the
Cys2-Hyp3 peptide bond. The lower cis-trans ratio for contryphan-Sm enabled
elucidation of the 3D structure of both its major and its minor forms, for which
the patterns of (3)J(H)(alpha)(HN) coupling constants are very different. As
with contryphan-R, the structure of the major form of contryphan-Sm (cis
Cys2-Hyp3 peptide bond) contains an N-terminal chain reversal and a C-terminal
type I beta-turn. The minor conformer (trans peptide bond) forms a hairpin
structure with sheetlike hydrogen bonds and a type II beta-turn, with the D-Trp4
at the 'Gly position' of the turn. The ratio of conformers arising from
cis-trans isomerism around the peptide bond preceding Hyp3 is sensitive to both
the amino acid sequence and the solution conditions, varying from 2.7:1 to 17:1
across the five sequences. The sequence and structural determinants of the
cis-trans isomerism have been elucidated by comparison of the cis-trans ratios
for these peptides with those for contryphan-R and an N-acetylated derivative
thereof. The cis-trans ratio is reduced for peptides in which either the charged
N-terminal ammonium or the X(5) side-chain carboxylate is neutralized, implying
that an electrostatic interaction between these groups stabilizes the cis
conformer relative to the trans. These results on the structures and cis-trans
equilibrium of different conformers suggest a paradigm of 'locally determined
but globally selected' folding for cyclic peptides and constrained protein
loops, where the series of stereochemical centers in the loop dictates the
favorable conformations and the equilibrium is determined by a small number of
side-chain interactions.
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Headers
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