Proteins searching for their target on DNA by one-dimensional diffusion: overcoming the “speed-stability” paradox

The sequence dependence of DNA-protein interactions that allows proteins to find the correct reaction site also slows down the 1D diffusion of the protein along the DNA molecule, leading to the so-called “speed-stability paradox,” wherein fast diffusion along the DNA molecule is seemingly incompatible with stable targeting of the reaction site. Here, we develop diffusion-reaction models that use discrete and continuous Gaussian random 1D diffusion landscapes with or without a high-energy cut-off, and two-state models with a transition to and from a “searching” mode in which the protein diffuses rapidly without recognizing the target. We show the conditions under which such considerations lead to a predicted speed-up of the targeting process, and under which the presence of a “searching” mode in a two-state model is nearly equivalent to the existence of a high-energy cut-off in a one-state model. We also determine the conditions under which the search is either diffusion-limited or reaction-limited, and develop quantitative expressions for the rate of successful targeting as a function of the site-specific reaction rate, the roughness of the DNA-protein interaction potential, and the presence of a “searching” mode. In general, we find that a rough landscape is compatible with a fast search if the highest energy barriers can be avoided by “hopping” or by the protein transitioning to a lower-energy “searching” mode. We validate these predictions with the results of Brownian dynamics, kinetic Metropolis, and kinetic Monte Carlo simulations of the diffusion and targeting process, and apply these concepts to the case of T7 RNA polymerase searching for its target site on T7 DNA.     

Asymmetric reduction of prochiral ketones to chiral alcohols catalyzed by plants tissue

As an important organic compound, chiral alcohols are the key chiral building blocks to many single enantiomer pharmaceuticals. Asymmetric reduction of the corresponding prochiral ketones to produce the chiral alcohols by biocatalysis is one of the most promising routes. Asymmetric reduction of different kinds of non-natural prochiral ketones catalyzed by various plants tissue was studied in this work. Acetophenone, 4'-chloroacetophenone and ethyl 4-chloroacetoacetate were chosen as the model substrates for simple ketone, halogen-containing aromatic ketone and beta-ketoesters, respectively. Apple (Malus pumila), carrot (Daucus carota), cucumber (Cucumis sativus), onion (Allium cepa), potato (Soanum tuberosum), radish (Raphanus sativus) and sweet potato (Ipomoea batatas) were chosen as the biocatalysts. It was found that these kinds of prochiral ketoness could be reduced by these plants tissue with high enantioselectivity. Both R- and S-form configuration chiral alcohols could be obtained. The e.e. and chemical yield could reach about 98 and 80% respectively for acetophenone and 4'-chloroacetophenone reduction reaction with favorable plant tissue. And the e.e. and yield for ethyl 4-chloroacetoacetate reduction reaction was about 91 and 45% respectively.     

Sesame Utilization in China: New Archaeobotanical Evidence from Xinjiang

Sesame Utilization in China: New Archaeobotanical Evidence from Xinjiang. A cache of sesame (Sesamum indicum L.) seeds, discovered in the Thousand Buddha Grottoes at Boziklik, Turpan, China, dating to ca. 700 years before present (BP), is hard evidence of their use in China since that time. Morphological and anatomical features suggest a white sesame cultivar. The sizeable quantity unearthed implies that sesame was a valued commodity that could provision the monks and enrich the diet of ancient inhabitants as an oil source.     

Genome Sequence of a Nicotine-Degrading Strain of Arthrobacter

We announce a 4.63-Mb genome assembly of an isolated bacterium that is the first sequenced nicotine-degrading Arthrobacter strain. Nicotine catabolism genes of the nicotine-degrading plasmid pAO1 were predicted, but plasmid function genes were not found. These results will help to better illustrate the molecular mechanism of nicotine degradation by Arthrobacter.