Nonspecifically bound proteins spin while diffusing along DNA

It is known that DNA-binding proteins can slide along the DNA helix while searching for specific binding sites, but their path of motion remains obscure. Do these proteins undergo simple one-dimensional (1D) translational diffusion, or do they rotate to maintain a specific orientation with respect to the DNA helix? We measured 1D diffusion constants as a function of protein size while maintaining the DNA-protein interface. Using bootstrap analysis of single-molecule diffusion data, we compared the results to theoretical predictions for pure translational motion and rotation-coupled sliding along the DNA. The data indicate that DNA-binding proteins undergo rotation-coupled sliding along the DNA helix and can be described by a model of diffusion along the DNA helix on a rugged free-energy landscape. A similar analysis including the 1D diffusion constants of eight proteins of varying size shows that rotation-coupled sliding is a general phenomenon. The average free-energy barrier for sliding along the DNA was 1.1 +/- 0.2 k(B)T. Such small barriers facilitate rapid search for binding sites.

Evidence for the formation of a known toxin, P-cresol, from menthofuran

Menthofuran (II, 4,5,6,7-tetrahydro-3,6-dimethyl benzofuran), the proximate toxin of R-(+)-pulegone (I), was administered orally to rats (200 mg/kg of body weight/day) for three days and the urinary metabolites were investigated. Among the several metabolites formed, two of them viz. 4-Hydroxy-4-methyl-2-cyclohexenone (VII) and p-cresol (VIII) were indentified. In support of the formation of these metabolites, it has been demonstrated that phenobarbital induced rat liver microsomes readily convert 4-methyl-2-cyclohexenone (V) to 4-hydroxy-4-methyl-2-cyclohexenone (VII) and p-cresol (VIII) in the presence of NADPH and O2. Possible mechanism for the formation of these two metabolites (VII, VIII) from menthofuran (II) has been proposed.

Studies on the metabolism of a monoterpene ketone, R-(+)-pulegone-a hepatotoxin in rat: isolation and characterization of new metabolites

1. The metabolic disposition of R-(+)-pulegone (1) was examined in rats following four daily oral doses (250 mg/kg). 2. Six metabolites, namely pulegol (II), 2-hydroxy-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanone (III), 3,6-dimethyl-7a-hydroxy-5,6,7,7a-tetrahydro-2(4H)-benzofuranone (IV), menthofuran (V), 5-methyl-2-(1-methyl-1-carboxyethylidene)cyclohexanone (VI), and 5-methyl-5-hydroxy-2-(1-hydroxy-1-carboxyethyl)cyclohexanone (VII) have previously been isolated from rat urine, and identified (Moorthy et al. (1989a). Eight new metabolites have now been isolated from rat urine, namely, 5-hydroxy-pulegone (VIII), piperitone (IX), piperitenone (X), 7-hydroxy-piperitone (XI), 8-hydroxy piperitone (XII), p-cresol (XIII), geranic acid (XIV) and neronic acid (XV). These were identified by n.m.r., i.r. and mass spectrometry. 3. Based on these results, metabolic pathways for the biotransformation of R-(+)-pulegone in rat have been proposed.

Time resolved terahertz spectroscopy of low frequency electronic resonances and optical pump-induced terahertz photoconductivity in reduced graphene oxide membrane

Towards ultrafast optoelectronic applications of single and a few layer reduced graphene oxide (RGO), we study time domain terahertz spectroscopy and optical pump induced changes in terahertz conductivity of self-supported RGO membrane in the spectral window of 0.5-3.5 THz. The real and imaginary parts of conductivity spectra clearly reveal low frequency resonances, attributed to the energy gaps due to the van Hove singularities in the density of states flanking the Dirac points arising due to the relative rotation of the graphene layers. Further, optical pump induced terahertz conductivity is positive, pointing to the dominance of intraband scattering processes. The relaxation dynamics of the photo-excited carriers consists of three cooling pathways: the faster (similar to 450 fs) one due to optical phonon emission followed by disorder mediated large momentum and large energy acoustic phonon emission with a time constant of a few ps (called the super-collision mechanism) and a very large time (similar to 100 ps) arising from the deep trap states. The frequency dependence of the dynamic conductivity at different delay times is analyzed in term of Drude-Smith model. (C) 2014 Published by Elsevier Ltd.