| Texto completo | |
| Autor(es): |
Vicente, Eduardo F.
[1]
;
Sahu, Indra D.
[2]
;
Crusca, Jr., Edson
[3, 4]
;
Basso, Luis G. M.
[5]
;
Munte, Claudia E.
[3]
;
Costa-Filho, Antonio J.
[5]
;
Lorigan, Gary A.
[2]
;
Cilli, Eduardo M.
[4]
Número total de Autores: 8
|
| Afiliação do(s) autor(es): | [1] Sao Paulo State Univ UNESP, Sch Sci & Engn, BR-17602496 Tupa, SP - Brazil
[2] Miami Univ, Dept Chem & Biochem, Oxford, OH 45056 - USA
[3] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil
[4] Sao Paulo State Univ UNESP, Inst Chem, BR-14800900 Araraquara, SP - Brazil
[5] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Fis, Lab Biofis Mol, BR-14040901 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Physical Chemistry B; v. 121, n. 49, p. 11085-11095, DEC 14 2017. |
| Citações Web of Science: | 1 |
| Resumo | |
Human dihydroorotate dehydrogenase (HsDHODH) enzyme has been studied as selective target for inhibitors to block the enzyme activity, intending to prevent proliferative diseases. The N-terminal microdomain seems to play an important role in the enzyme function. However, the molecular mechanism of action and dynamics of this region are not totally understood yet. This study analyzes the interaction and conformation in model membranes of HsDHODH microdothain using peptide, analogues containing the paramagnetic amino acid TOAC at strategic positions. In buffer solution, the analogues presented a disordered conformation, but acquired a high content of alpha-helical structure in membrane mimetics, which was found to be lipid dependent. The microdomain peptide structure in micelles showed a very different peptide conformation when compared to the reported crystal structure, displaying a conformational flexibility of its helices, promoted by the connecting loop, which might be functionally relevant. Electron spin resonance in membrane compositions containing POPC, POPE, and cardiolipin showed that interaction of the analogues was enhanced by the presence of cardiolipin, indicating that the microdomain preferentially interacts with cardiolipin-containing membranes. Therefore, the great flexibility of the microdomain and the cardiolipin affinity should be considered in further studies aimed at finding new inhibitory compounds to fight proliferative diseases. (AU) | |
| Processo FAPESP: | 10/12953-4 - Aplicação da RMN na elucidação estrutural dos domínios C-terminais das septinas SEPT2 e SEPT4 e interação com a proteína alfa-sinucleína |
| Beneficiário: | Edson Crusca Junior |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 14/00206-0 - Estrutura e função dos peptídeos de fusão da glicoproteína spike do SARS-CoV |
| Beneficiário: | Luís Guilherme Mansor Basso |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 10/06526-6 - Uso de peptídeos sintéticos no estudo da proteína DHODH e do peptídeo de fusão do vírus da Dengue. |
| Beneficiário: | Eduardo Maffud Cilli |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 15/18390-5 - Ressonância magnética eletrônica em biofísica molecular: novos e velhos olhares para novos e velhos problemas |
| Beneficiário: | Antonio José da Costa Filho |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |