RESUMO
Inhibition of the Tryparedoxin peroxidase interaction has been becomes a new therapeutic strategy in leishmaniasis. Docking analysis was carried out to study the effects of quercetin and taxifolin on Tryparedoxin Peroxidase (TryP). Tryparedoxin peroxidase of Trypanosomatidae functions as antioxidants through their Peroxidase and peroxynitrite reductase activities. The 3D models of Tryparedoxin Peroxidase of Leishmania braziliensis (L. braziliensis TryP) was modeled using the template Tryparedoxin Peroxidase I from Leishmania Major (L. Major TryPI) (PDB ID: 3TUE). Further, we evaluated for TryP inhibitory activity of flavonoids such as quercetin and taxifolin using in silico docking studies. Docking results showed the binding energies of - 11.8601and -8.0851 for that quercetin and taxifolin respectively. Flavonoids contributed better L. braziliensis TryP inhibitory activity because of its structural parameters. Thus, from our in silico studies we identify that quercetin and taxifolin posses anti-leishmanial acitivities mediated through TryP inhibition mechanism.
RESUMO
The current article describes the biophysical characterization and folding studies of fibroblast growth factor homologous factor-1b (FHF-1b) in comparison with acidic fibroblast growth factor (FGF-1). Our data indicates that FHF-1 is significantly more stable than FGF-1. The folding mechanism of these two proteins seems to be different although they share high degree of sequence and structural similarity. FHF-1 unfolds through stable intermediate state while unfolding of FGF-1 is two-state. Interestingly, low concentration of sodium dodecyl sulfate (SDS) drives the folding pathway of FHF-1b to two-state.
Assuntos
Fatores de Crescimento de Fibroblastos/química , Dobramento de Proteína , Sequência de Aminoácidos , Fator 1 de Crescimento de Fibroblastos/química , Fator 1 de Crescimento de Fibroblastos/genética , Fator 1 de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Dados de Sequência Molecular , Ligação Proteica , Alinhamento de Sequência , Dodecilsulfato de Sódio , TensoativosRESUMO
The effect of methanol and trifluoroethanol (TFE) on the structure and folding of molten globule state of procerain, a cysteine protease from Calotropis procera, was studied by circular dichroism spectroscopy. The magnitude of ellipticity at 215 nm, as a measure of beta-sheet content, is dependent on the concentration of the TFE. Interestingly, a switch over from the beta-sheet structure of the molten globule state to alpha-helix was observed at 60% TFE and the ellipticity at 222 nm increased as a function of TFE concentration beyond this critical TFE concentration. Temperature induced unfolding of the molten globule state of procerain in 10% methanol showed stabilization of alpha-rich domain with concomitant destabilization of beta-rich domain. Using higher concentration of methanol (20-40 %) had no stabilizing effect on the alpha-rich domain however, the beta-rich domain was destabilized, indicating that the stability of the domains were not interdependent and that a low concentration of methanol induced stabilization in alpha-rich domain.
