8 research outputs found
Inhibition of viral group-1 and group-2 neuraminidases by oseltamivir: A comparative structural analysis by the ScrewFit algorithm
Inhibition of viral group-1 and group-2 neuraminidases by oseltamivir: A comparative structural analysis by the ScrewFit algorithm
The viral surface glycoprotein neuraminidase (NA) allows the influenza virus penetration and the egress of virions. NAs are classified as A, B, and C. Type-A NAs from influenza virus are subdivided into two phylogenetically distinct families, group-1 and group-2. NA inhibition by oseltamivir represents a therapeutic approach against the avian influenza virus H5N1. Here, structural bases for oseltamivir recognition by group-1 NA1, NA8 and group-2 NA9 are highlighted by the ScrewFit algorithm for quantitative structure comparison. Oseltamivir binding to NA1 and NA8 affects the geometry of Glu119 and of regions Arg130-Ser160, Val240-Gly260, and Asp330-Glu382, leading to multiple NA conformations. Additionally, although NA1 and NA9 share almost the same oseltamivir-bound final conformation, they show some relevant differences as suggested by the ScrewFit algorithm. These results indicate that the design of new NA inhibitors should take into account these family-specific effects induced on the whole structure of NAs
Inhibition of viral group-1 and group-2 neuraminidases by oseltamivir: A comparative structural analysis by the ScrewFit algorithm
The viral surface glycoprotein neuraminidase (NA) allows the influenza virus penetration and the egress of virions. NAs are classified as A. B, and C. Type-A NAs from influenza virus are subdivided into two phylogenetically distinct families, group-1 and group-2. NA inhibition by oseltamivir represents a therapeutic approach against the avian influenza virus H5N1. Here, structural bases for oseltamivir recognition by group-1 NA1, NA8 and group-2 NA9 are highlighted by the ScrewFit algorithm for quantitative structure comparison. Oseltamivir binding to NA1 and NA8 affects the geometry of Glu119 and of regions Arg130-Ser160, Val240-Gly260, and Asp330-Glu382, leading to multiple NA conformations. Additionally, although NA1 and NA9 share almost the same oseltamivir-bound final conformation, they show some relevant differences as suggested by the ScrewFit algorithm. These results indicate that the design of new NA inhibitors should take into account these family-specific effects induced on the whole structure of NAs. (C) 2009 Elsevier B.V. All rights reserved
Transformation of white poplar (Populus alba L.) with a novel Arabidopsis thaliana cysteine proteinase inhibitor gene and analysis of insect pest resistance
Transgenic white poplar (Populus alba L.) plants expressing a novel Arabidopsis thaliana cysteine proteinase
inhibitor (Atcys) gene have been produced using Agrobacterium tumefaciens-mediated gene transfer. Internodal
stem segments of cv. Villafranca were co-cultivated with the EHA105 pBI-Atcys A. tumefaciens strain. Sixteen
putative transgenic plant lines were regenerated from different calli with a transformation efficiency of 11%. The
integration and expression of the cysteine proteinase inhibitor (Atcys) gene into the plant genome was confirmed
by Southern and northern blot analyses. Papain inhibitory activity was detected in poplar transgenic tissues by
means of a specific in vitro assay. Such activity was sufficient to inhibit most of the digestive proteinase activity of
chrysomelid beetle (Chrysomela populi L.) and confer resistance to C. populi larvae on selected transgenic plants.
A close correspondence between the inhibition of papain and resistance to poplar leaf beetle was observed in all
tested transgenic lines. Our results indicate that Atcys could be succesfully employed in breeding programmes
aimed at the selection of new poplar genotypes resistant to major insect pests
Design, Synthesis, Antibacterial Potential, and Structural Characterization of N-Acylated Derivatives of the Human Autophagy 16 Polypeptide
Multiple scale dynamics in proteins probed at multiple time scales through fluctuations of NMR chemical shifts
International audience: Fluctuations of NMR resonance frequency shifts and their relation with protein exchanging conformations are usually analysed in terms of simple two-site jump processes. However, this description is unable to account for the presence of multiple time scale dynamics. In this work, we present an alternative model for the interpretation of the stochastic processes underlying these fluctuations of resonance frequencies. Time correlation functions of (15)N amide chemical shifts computed from molecular dynamics simulations (MD) were analysed in terms of a transiently fractional diffusion process. The analysis of MD trajectories spanning dramatically different time scales (~200 ns and 1ms [Shaw, D. E. et al. Science, 2010, 330, 341-346]) allowed us to show that our model could capture the multiple scale structure of chemical shift fluctuations. Moreover, the predicted exchange contribution Rex to the NMR transverse relaxation rate is in qualitative agreement with experimental results. These observations suggest that the proposed fractional diffusion model may provide significative improvement to the analysis of NMR dispersion experiments