1DFY

NMR STRUCTURE OF CONTRYPHAN-SM CYCLIC PEPTIDE (MAJOR FORM-CIS)

1DFY の概要

• エントリーDOI: 10.2210/pdb1dfy/pdb
• 関連するPDBエントリー: 1DFZ 1DG0 1QFB
• 分子名称: CONTRYPHAN-SM (1 entity in total)
• 機能のキーワード: cyclic peptide, disulfide bridge, d-tryptophan, cis-trans isomerism, contryphan, toxin
• 由来する生物種: Conus stercusmuscarum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 991.15

構造登録者

Pallaghy, P.K.,He, W.,Jimenez, E.C.,Olivera, B.M.,Norton, R.S. (登録日: 1999-11-22, 公開日: 2002-05-01, 最終更新日: 2025-03-26)

主引用文献

Pallaghy, P.K.,He, W.,Jimenez, E.C.,Olivera, B.M.,Norton, R.S.
Structures of the contryphan family of cyclic peptides. Role of electrostatic interactions in cis-trans isomerism.
Biochemistry, 39:12845-12852, 2000

PubMed Abstract: 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.

PubMed: 11041849
DOI: 10.1021/bi0010930

実験手法

SOLUTION NMR