Conformational multiplicity of bacterial ferric binding protein revealed by small angle x-ray scattering and molecular dynamics calculations

This study combines molecular dynamics (MD) simulations with small angle x-ray scattering (SAXS) measurements to investigate the range of conformations that can be adopted by a pH/ionic strength (IS) sensitive protein and to quantify its distinct populations in solution. To explore how the conformational distribution of proteins may be modified in the environmental niches of biological media, we focus on the periplasmic ferric binding protein A (FbpA) from Haemophilus influenzae involved in the mechanism by which bacteria capture iron from higher organisms. We examine iron-binding/release mechanisms of FbpA in varying conditions simulating its biological environment. While we show that these changes fall within the detectable range for SAXS as evidenced by differences observed in the theoretical scattering patterns calculated from the crystal structure models of apo and holo forms, detection of conformational changes due to the point mutation D52A and changes in ionic strength (IS) from SAXS scattering profiles have been challenging. Here, to reach conclusions, statistical analyses with SAXS profiles and results from different techniques were combined in a complementary fashion. The SAXS data complemented by size exclusion chromatography point to multiple and/or alternative conformations at physiological IS, whereas they are well-explained by single crystallographic structures in low IS buffers. By fitting the SAXS data with unique conformations sampled by a series of MD simulations under conditions mimicking the buffers, we quantify the populations of the occupied substates. We also find that the D52A mutant that we predicted by coarse-grained computational modeling to allosterically control the iron binding site in FbpA, responds to the environmental changes in our experiments with conformational selection scenarios that differ from those of the wild type

The Effects Of Trimetazidine And Sildenafil On Bilateral Cavernosal Nerve Injury Induced Oxidative Damage And Cavernosal Fibrosis In Rats

Aim. The aim of this study was to compare the effects of sildenafil and trimetazidine on bilateral cavernosal nerve injury-induced oxidative damage and fibrotic changes in cavernosal tissue in rat model. Material and Methods. A total of 32 male Sprague-Dawley rats were randomly divided into 4 groups; each group consist 8 rats (control, BCI, BCI + TMZ, and BCI + sildenafil groups). Tissue superoxide dismutase (SOD), malondialdehyde (MDA), and protein carbonyl (PC) levels were determined biochemically and distribution of cavernosal fibrosis density among groups was performed histopathologically. Results. Tissue SOD levels in BCI group were significantly lower than the control group (P < 0.05). Tissue MDA and PC levels in BCI group were significantly higher than the control group (P < 0.05). TMZ and sildenafil administration significantly increased tissue SOD levels (P < 0.05) and reduced tissue MDA and PC levels (P < 0.05). Histologically, the degree of cavernosal fibrosis and collagen density was higher in BCI group in comparison to control, TMZ-treated, and sildenafil-treated groups. Conclusion. BCI caused oxidative damage and increased cavernosal fibrosis in rat penis. TMZ and sildenafil treatment decreased oxidative damage and reduced the degree of fibrosis in penile tissue due to BCI

Superiority of semiclassical over quantum mechanical calculations

for a three-dimensional syste

The Autonomy of the State, Radical Left and Karatani's Capital‐Nation‐State: The Turkish Left of 1960‐1971

The purpose of this paper is to provide an account of how leading radical left movements of Turkey in 1960–71 conceptualized the state. The analytical framework draws on the mode of exchange framework developed by Kojin Karatani. The Turkish Left was unable to theorize the autonomy of the state, the construction of the nation as an imagined community, and the importance of popular resistance against the state's destruction of traditional communities. Right-wing political parties filled this vacuum with the populist discourse of nation. The Turkish Left conceded its social base to right-wing parties and hence lost the opportunity of winning political efficacy. Our critical assessment of the Left of Turkey in 1960–71 is pertinent to discussions about present-day left-wing strategies that leave the nation and ravaged communities to right parties to exploit or utilise as part of their program