Probing the transition state of the allosteric pathway of the Shaker Kv channel pore by linear free-energy relations.
ABSTRACT Long-range coupling between distant functional elements of proteins may rely on allosteric communication trajectories lying along the protein structure, as described in the case of the Shaker voltage-activated potassium (Kv) channel model allosteric system. Communication between the distant Kv channel activation and slow inactivation pore gates was suggested to be mediated by a network of local pairwise and higher-order interactions among the functionally unique residues that constitute the allosteric trajectory. The mechanism by which conformational changes propagate along the Kv channel allosteric trajectory to achieve pore opening, however, remains unclear. Such conformational changes may propagate in either a concerted or a sequential manner during the reaction coordinate of channel opening. Residue-level structural information on the transition state of channel gating is required to discriminate between these possibilities. Here, we combine patch-clamp electrophysiology recordings of Kv channel gating and analysis using linear free-energy relations, focusing on a select set of residues spanning the allosteric trajectory of the Kv channel pore. We show that all allosteric trajectory residues tested exhibit an open-like conformation in the transition state of channel opening, implying that coupling interactions occur along the trajectory break in a concerted manner upon moving from the closed to the open state. Energetic coupling between the Kv channel gates thus occurs in a concerted fashion in both the spatial and the temporal dimensions, strengthening the notion that such trajectories correspond to pathways of mechanical deformation along which conformational changes propagate.
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ABSTRACT: The occurrence and distribution of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in a typical process of production of 1,4-dichlorobenzene (p-DCB) were investigated systematically in this study. P5CDFs and H6CDFs were the main congeners of PCDD/Fs, while only low levels of other PCDD/Fs were detected in the samples. The concentrations of PCBs were up to 4614 ng/g in the semi-manufactured products, and 1797 ng/g in the product p-DCB. It was also found that high chlorinated PCB congeners increased with the further chlorination. The levels of PCDD/Fs decreased obviously in the purification process, while PCBs could not be removed effectively. Polychlorophenols and other important dioxin precursors (1,4-dichloro-2-phenoxybenzene and 2-phenyl-2',5,5'-trichlorophenol) were also analyzed. Polychlorophenols which ortho- and para-positions of the hydroxyl were substituted by chlorine were the main congeners. In addition, a possible pathway of the formation of PCDD/Fs and PCBs in the production of p-DCB was presented. The results of this article suggest that re-estimation on the risk of using p-DCB products, especially the products for daily use such as mothballs, is expected.Chemosphere 01/2005; 57(10):1317-23. · 3.14 Impact Factor
Chapter: Properties of Liquids and Gases[show abstract] [hide abstract]
ABSTRACT: Liquids are distinguished from solids by the fact that their particles are readily displaced. Whereas forces of finite magnitude are required to deform a solid, no force at all is required to alter the shape of a liquid, provided only that sufficient time is allowed for the change of shape to take place. When the shape is altered quickly, liquids do display a resistance, but this vanishes very quickly after the motion is finished. This ability of liquids to oppose a change in shape is called viscosity. We will discuss viscosity in depth in Section 4.2. As well as the usual liquids that are easy to move, there are also very viscous liquids whose resistance to change of shape is considerable, but which vanishes again at rest. Starting out from the viscous state, all phase transitions to (amorphous) solid bodies are possible. Heated glass, for example, passes through all possible transitions; in asphalt and similar substances these transitions occur at normal temperatures. For example, depending on the temperature, if a barrel of asphalt is tipped over, the asphalt will flow out within a few days or weeks. The mass that flows out forms a flat cake. Although it continually flows, one can walk on it without making footprints. Footprints will be left, however, if one stands still for a longer time on the asphalt. Hammering on the asphalt causes the mass to shatter like glass. In the study of the equilibrium of liquids, we consider states of rest or sufficiently slow motion. The resistance to change of shape may then be set to zero, and we obtain a definition of the liquid state: In a liquid in equilibrium, all resistance to change of shape is equal to zero.06/2010: pages 15-42;
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ABSTRACT: There are no longer any large scale uses of pentachlorobenzene (PeCB). Current emissions of PeCB to the environment are estimated to be about 121000kgy(-1), based on published information. The largest sources appear to be combustion of solid wastes, 32000kgy(-1), biomass burning, 45000kgy(-1) with degradation of an agricultural fungicide, quintozene, contributing 26000kgy(-1) and industrial releases less important. PeCB has been measured in many environmental media over the past 35 years. Low but detectable concentrations of PeCB have been reported in the atmosphere, sediments and biota in remote areas of the world. Calculations using a global distribution model are consistent with the estimate of approximately 100000kgy(-1) global PeCB emissions. Concentrations of PeCB in the environment have declined with a 90% decrease of PeCB concentrations in herring gull eggs from Lake Superior, Canada since 1979.Chemosphere 04/2009; 75(5):555-64. · 3.14 Impact Factor