Interfacial Inhibitors

The X-ray crystallographic analysis of T2R crystals soaked with vinblastine has revealed its binding site between the two tubulins of this short protofilament-like curved assembly (Fig. 6) [55]. It is equally contributed by the a-subunit of one tubulin and the [i-subuni I of the other. Vinblastine therefore belongs to the growing class of small molecules ligands known as interfacial inhibitors [58] these... 

Demulsifiers (specifically, oil spill demulsifiers) can be applied to oil spills in low concentrations. They prevent mousse formation for significant periods of time and cause a large reduction in oil-water interfacial tension. The best of these was found to prevent emulsification at dosages as low as 1 part inhibitor to 20,000 parts of fresh oil at 20° C [273]. At dosages of 1 1000, at temperatures higher than 10° C, the chemical also results in significant and rapid dispersion of the oil. For very low temperatures or highly weathered oil, the performance of the chemical falls off sharply. 

Selected entries from Methods in Enzymology [vol, page(s)] Add-base catalysis [with site-directed mutants, 249, 110-118 altered pH dependencies, 249, 110] commitment to [in determination of intrinsic isotope effects, 249, 343, 347-349 in interfacial catalysis, 249, 598-599 equilibrium isotope exchange in, 249, 443-479 hydrogen tunneling in, 249, 373-397] interfacial [competitive inhibitors, kinetic characterization, 249, 604-605 equilibrium parameters, 249, 587-594 forward commitment to, 249, 598-599 interpretation, 249, 578-586 (constraining variables for high processivity, 249, 582-586 kinetic variables at interface,... 

Reaction of dissolved gases in clouds occurs by the sequence gas-phase diffusion, interfacial mass transport, and concurrent aqueous-phase diffusion and reaction. Information required for evaluation of rates of such reactions includes fundamental data such as equilibrium constants, gas solubilities, kinetic rate laws, including dependence on pH and catalysts or inhibitors, diffusion coefficients, and mass-accommodation coefficients, and situational data such as pH and concentrations of reagents and other species influencing reaction rates, liquid-water content, drop size distribution, insolation, temperature, etc. Rate evaluations indicate that aqueous-phase oxidation of S(IV) by H2O2 and O3 can be important for representative conditions. No important aqueous-phase reactions of nitrogen species have been identified. Examination of microscale mass-transport rates indicates that mass transport only rarely limits the rate of in-cloud reaction for representative conditions. Field measurements and studies of reaction kinetics in authentic precipitation samples are consistent with rate evaluations. 

In lipases the existing database regarding the oxyanion holes is still limited. In RmL two amide groups (residues 145 and 146) were originally proposed as likely candidates for this function (Brady et al., 1990). However, structural analyses of the two RmL-inhibitor complexes (Brzozowski et al., 1991 U. Derewenda et al., 1992) revealed that the oxyanion hole is likely to be fully formed only after the conformational change associated with interfacial activation, and that it is made up of both the amide and the side-chain hydroxyl of Ser-82 (Fig. 6). A hy-... 

In GcL Schrag et al. (1991) postulate that Ala-218 (again structurally equivalent to 145 in RmL) and Ala-132 play the same role in the stabilization of the intermediates. However, assuming that conformational rearrangements will also occur in this lipase during interfacial activation, the confirmation of this proposal will have to await a structural description of an enzyme-inhibitor complex. 

In the TSA and substrate-based inhibitor complexes, the sn-1 and 5m-2 hydrocarbon chains lie in a hydrophobic channel that extends from the active site to the surface of the enzyme. If the lengths of the hydrocarbon moieties were increased from the 7 to 8 carbons present in the model compounds to that of natural substrates (commonly 14 to 18 carbons long), they would protrude from the enzyme surface. It is probably safe to assume that these hydrophobic tails remain imbedded in the membrane during interfacial catalysis in order to minimize the energetic costs of substrate transfer. Thus the adsorption surface chosen by Scott et al. (1990a), which envelops the hydrophobic channel, is the most likely surface to contact the bulk phase lipid directly. 

Brzozowski, A. M., Derewenda, U., Derewenda, Z. S., Dodson, G. G., Lawson, D. M., Turkenburg, j. P., Bjorkling, F., Huge-jensen, B., Patkar,S. A.,andThim, L. (1991). A model for interfacial activation in lipases from the structure of a fungal lipase-inhibitor complex. Nature (London) 351, 491-494. 

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