| Texto completo | |
| Autor(es): |
Feliciano, Patricia R.
;
Drennan, Catherine L.
;
Cristina Nonato, M.
Número total de Autores: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 113, n. 35, p. 6-pg., 2016-08-30. |
| Resumo | |
Fumarate hydratases (FHs) are essential metabolic enzymes grouped into two classes. Here, we present the crystal structure of a class I FH, the cytosolic FH from Leishmania major, which reveals a previously undiscovered protein fold that coordinates a catalytically essential [4Fe-4S] cluster. Our 2.05 angstrom resolution data further reveal a dimeric architecture for this FH that resembles a heart, with each lobe comprised of two domains that are arranged around the active site. Besides the active site, where the substrate S-malate is bound bidentate to the unique iron of the [4Fe-4S] cluster, other binding pockets are found near the dimeric enzyme interface, some of which are occupied bymalonate, shown here to be a weak inhibitor of this enzyme. Taken together, these data provide a framework both for investigations of the class I FH catalytic mechanism and for drug design aimed at fighting neglected tropical diseases. (AU) | |
| Processo FAPESP: | 08/08262-6 - Caracterização cinética, estrutural e funcional dos genes LmjF24.0320. e LmjF29.1960 que codificam a enzima fumarato hidratase em Leishmania major |
| Beneficiário: | Maria Cristina Nonato |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 11/19674-6 - Determinação da estrutura cristalográfica das isoformas fumarato hidratase de Leishmania major |
| Beneficiário: | Patrícia Rosa Feliciano |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |
| Processo FAPESP: | 09/10454-3 - Estudos da correlação entre estrutura e função da enzima fumarato hidratase em Leishmania major |
| Beneficiário: | Patrícia Rosa Feliciano |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |