1dg0
From Proteopedia
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NMR STRUCTURE OF DES[GLY1]-CONTRYPHAN-R CYCLIC PEPTIDE (MAJOR FORM)
Overview
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.
About this Structure
1DG0 is a Protein complex structure of sequences from Conus radiatus. Full crystallographic information is available from OCA.
Reference
Structures of the contryphan family of cyclic peptides. Role of electrostatic interactions in cis-trans isomerism., Pallaghy PK, He W, Jimenez EC, Olivera BM, Norton RS, Biochemistry. 2000 Oct 24;39(42):12845-52. PMID:11041849
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