How C-Terminal Carboxyamidation Alters the Biological Activity of Peptides from the Venom of the Eumenine Solitary Wasp

Maurício L. Sforça, Sérgio Oyama, Fernanda Canduri, Carla C B Lorenzi, Thelma A. Pertinhez, Katsuhiro Konno, Bibiana M. Souza, Mário S. Palma, J. Ruggiero Neto, Walter F. Azevedo, Alberto Spisni

Research output: Contribution to journalArticle

Abstract

Inflammatory peptides display different types of post-transcriptional modifications, such as C-terminal amidation, that alter their biological activity. Here we describe the structural and molecular dynamics features of the mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF-NH 2), found in the venom of the solitary wasp, and of its carboxyl-free C-terminal form (EMP-AF-COO-) characterized by a reduced activity. Circular dichroism indicates that both peptides switch from a random coil conformation in water to a helical structure in TFE and SDS micelles. NMR data, in 30% TFE, reveal that the two peptides fold into an α-helix spanning most of their length, while they differ in terms of molecular rigidity. To understand the origins of the conformational flexibility observed in the case of EMP-AF-COO-, a 5 ns MD simulation was carried out for each peptide, in an explicit water/TFE environment. The results show that the two peptides differ in an H-bond between Leu14 NH2 and the backbone carbonyl of Ile11. The loss of that H-bond in EMP-AF-COO - leads to a significant modification of its structural dynamics. In fact, as evidenced by essential dynamics analysis, while EMP-AF-NH2 exists mainly as a rigid structure, EMP-AF-COO- presents two helical stretches that fluctuate in some sort of independent fashion. We conclude that the diverse biological activity of the two peptides is not simply due to the reduction of the net positive charge, as generally suggested, but also to a structural perturbation of the amphipathic α-helix that affects their ability to perturb the cell membrane.

Original languageEnglish
Pages (from-to)5608-5617
Number of pages10
JournalBiochemistry
Volume43
Issue number19
DOIs
Publication statusPublished - May 18 2004

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Wasps
Venoms
Bioactivity
Peptides
Polytetrafluoroethylene
Structural dynamics
Furylfuramide
Wasp Venoms
Rigid structures
Water
Micelles
Molecular Dynamics Simulation
Cell membranes
Circular Dichroism
eumenine mastoparan-AF
Rigidity
Dynamic analysis
Conformations
Molecular dynamics
Switches

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sforça, M. L., Oyama, S., Canduri, F., Lorenzi, C. C. B., Pertinhez, T. A., Konno, K., ... Spisni, A. (2004). How C-Terminal Carboxyamidation Alters the Biological Activity of Peptides from the Venom of the Eumenine Solitary Wasp. Biochemistry, 43(19), 5608-5617. https://doi.org/10.1021/bi0360915

How C-Terminal Carboxyamidation Alters the Biological Activity of Peptides from the Venom of the Eumenine Solitary Wasp. / Sforça, Maurício L.; Oyama, Sérgio; Canduri, Fernanda; Lorenzi, Carla C B; Pertinhez, Thelma A.; Konno, Katsuhiro; Souza, Bibiana M.; Palma, Mário S.; Neto, J. Ruggiero; Azevedo, Walter F.; Spisni, Alberto.

In: Biochemistry, Vol. 43, No. 19, 18.05.2004, p. 5608-5617.

Research output: Contribution to journalArticle

Sforça, ML, Oyama, S, Canduri, F, Lorenzi, CCB, Pertinhez, TA, Konno, K, Souza, BM, Palma, MS, Neto, JR, Azevedo, WF & Spisni, A 2004, 'How C-Terminal Carboxyamidation Alters the Biological Activity of Peptides from the Venom of the Eumenine Solitary Wasp', Biochemistry, vol. 43, no. 19, pp. 5608-5617. https://doi.org/10.1021/bi0360915
Sforça, Maurício L. ; Oyama, Sérgio ; Canduri, Fernanda ; Lorenzi, Carla C B ; Pertinhez, Thelma A. ; Konno, Katsuhiro ; Souza, Bibiana M. ; Palma, Mário S. ; Neto, J. Ruggiero ; Azevedo, Walter F. ; Spisni, Alberto. / How C-Terminal Carboxyamidation Alters the Biological Activity of Peptides from the Venom of the Eumenine Solitary Wasp. In: Biochemistry. 2004 ; Vol. 43, No. 19. pp. 5608-5617.
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