Significance of D- tryptophan in Contryphan-Ar1131 Conus peptide: Oxidative folding, trypsin binding, and photostabilization activity

Moi, Smriti; Shekh, Shamasoddin; Dolle, Ashwini; Vijayasarathy, Marimuthu; Gowd, Konkallu Hanumae

doi:10.1016/j.peptides.2022.170845

Cited by 3 publications

(1 citation statement)

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“…In addition to the naïve redox conopeptides derived from the transcriptome, additional putative peptides having 4- trans hydroxylation of proline have been chemically synthesized to assess the influence of post-translational modification of proline on the oxidative folding of conotoxins. The reversal of the configuration of tryptophan residues in contryphans and post-translational modifications of proline residues in various conotoxins have been demonstrated to assist the oxidative folding of conotoxins. , The report evaluated the catalytic activity of new redox conopeptides using α-conotoxin ImI as a model peptide. Computational methods using density functional theory (DFT) and 2D-NMR methods have been implemented to probe the structural features of new redox conopeptides.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Folding Catalysts of Conotoxins Derived from the Venom Duct Transcriptome of C. frigidus and C. amadis

Shekh,

Dhurjad,

Vijayasarathy

et al. 2023

Biochemistry

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Two novel redox conopeptides with proline residues outside and within the active site disulfide loop were derived from the venom duct transcriptome of the marine cone snails Conus f rigidus and Conus amadis. Mature peptides with possible posttranslational modification of 4-trans-hydroxylation of proline, namely, Fr874, Fr890[P1O], Fr890[P2O], Fr906, Am1038, and Am1054, have been chemically synthesized and characterized using mass spectrometry. The estimated reduction potential of cysteine disulfides of synthetic peptides varied from −298 to −328 mV, similar to the active site cysteine disulfide motifs of the redox family of proteins. Fr906/Am1054 exhibited pronounced catalytic activity and assisted in improving the yields of natively folded globular form α-conotoxin ImI. Three-dimensional (3D) structures of the redox conopeptides were optimized using computational methods and verified by 2D-ROESY NMR spectroscopy: C. f rigidus peptides adopt an N-terminal helical fold and C. amadis peptides adopt distinct structures based on the Phe4−Pro/Hyp5 peptide bond configuration. The shift in the cis−trans configuration of the Phe4− Pro/Hyp5 peptide bond of Am1038/Am1054 was observed between reduced free thiol and oxidized disulfide forms of the optimized peptides. The report confirms the position-specific effect of hydroxyproline on the oxidative folding of conotoxins and sequence diversity of redox conopeptides in the venom duct of cone snails.

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Section: Introductionmentioning

confidence: 99%