Structural and functional characterization of a multifunctional alanine-rich peptide analogue from Pleuronectes americanus
| Autor: | Carolina Rodrigues Costa, Octavio L. Franco, Marcelo P. Bemquerer, Maysa Paula da Costa, Lidia M. P. Lima, Paula Danyelle Almeida da Silva, Sonia Maria de Freitas, Osmar N. Silva, João Alexandre Ribeiro Gonçalves Barbosa, Diego O. Nolasco, Maria Teresa Villela Romanos, Beatriz Simas Magalhães, Ludovico Migliolo, Maria do Rosário Rodrigues Silva |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Proteomics
Protein Structure Protein Folding Staphylococcus aureus Circular dichroism Erythrocytes Science Biophysics Peptide Flounder Molecular Dynamics Candida parapsilosis medicine.disease_cause Biochemistry Cell Line chemistry.chemical_compound Computational Chemistry Trichophyton Antifreeze protein Biochemical Simulations Peptide synthesis medicine Synthetic Peptide Animals Humans Biology Escherichia coli Candida Alanine chemistry.chemical_classification Multidisciplinary biology Chemistry Proteins Computational Biology HCT116 Cells biology.organism_classification In vitro Medicine Biophysic Al Simulations Caco-2 Cells Peptides Research Article |
| Zdroj: | PLoS ONE, Vol 7, Iss 10, p e47047 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Recently, defense peptides that are able to act against several targets have been characterized. The present work focuses on structural and functional evaluation of the peptide analogue Pa-MAP, previously isolated as an antifreeze peptide from Pleuronectes americanus. Pa-MAP showed activities against different targets such as tumoral cells in culture (CACO-2, MCF-7 and HCT-116), bacteria (Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 25923), viruses (HSV-1 and HSV-2) and fungi (Candida parapsilosis ATCC 22019, Trichophyton mentagrophytes (28d&E) and T. rubrum (327)). This peptide did not show toxicity against mammalian cells such as erythrocytes, Vero and RAW 264.7 cells. Molecular mechanism of action was related to hydrophobic residues, since only the terminal amino group is charged at pH 7 as confirmed by potentiometric titration. In order to shed some light on its structure-function relations, in vitro and in silico assays were carried out using circular dichroism and molecular dynamics. Furthermore, Pa-MAP showed partial unfolding of the peptide changes in a wide pH (3 to 11) and temperature (25 to 95°C) ranges, although it might not reach complete unfolding at 95°C, suggesting a high conformational stability. This peptide also showed a conformational transition with a partial α-helical fold in water and a full α-helical core in SDS and TFE environments. These results were corroborated by spectral data measured at 222 nm and by 50 ns dynamic simulation. In conclusion, data reported here show that Pa-MAP is a potential candidate for drug design against pathogenic microorganisms due to its structural stability and wide activity against a range of targets. |
| Databáze: | OpenAIRE |
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