The discovery of the myriad roles of carbohydrates in biological recognition phenomena has led to an increased demand for practical routes to gram-scale quantities of unnatural carbohydrate structures. We have investigated the applicability of enzymes as catalysts for mono-oligo-, and polysaccharide synthesis. Here, we review our progress in the area, in particular the use of aldolases for monosaccharide synthesis, the synthesis of the activated sugar nucleosides required for Leloir-pathway glycosidic bond formation, and the use of both Leloir-and non-Leloir-pathway enzymes for the synthesis of carbohydrate polymers.
DNA glycosylases preserve the integrity of genetic information by recognizing damaged bases in the genome and catalyzing their excision. It is unknown how DNA glycosylases locate covalently modified bases hidden in the DNA helix amongst vast numbers of normal bases. Here we employ atomic-force microscopy (AFM) with carbon nanotube probes to image search intermediates of human 8-oxoguanine DNA glycosylase (hOGG1) scanning DNA. We show that hOGG1 interrogates DNA at undamaged sites by inducing drastic kinks. The sharp DNA bending angle of these non-lesion-specific search intermediates closely matches that observed in the specific complex of 8-oxoguanine-containing DNA bound to hOGG1. These findings indicate that hOGG1 actively distorts DNA while searching for damaged bases.
The San Andreas Fault (SAF) is weak in an absolute sense, in that it moves under shear stresses far smaller than implied by the most obvious reading of laboratory friction results (Byerlee law with hydrostatic pore pressure and friction coefficient F = 0.6-0.9). It is also weak in a relative sense, in that the adjoining crust seems to be mechanically stronger; this is implied by the stress state there having a horizontal maximum principal direction that makes a steep angle to the trace of the SAF, much larger than the 25-30° angle (i.e., 45° - 0.5 arctan F) expected from standard frictional failure considerations, and in the range of 60° to nearly 90°. It is shown that a maturely deformed fault zone which is weak relative to its surroundings, owing to inherent material strength and/or pore pressure differences, develops stresses within it which are distinct from those of its surroundings. Because of those stress differences, it is found that pore pressure distributions which are high, and near to the fault-normal compressive stress, within the fault zone, but which decrease with distance into the adjacent crust, are consistent with both the absolute and relative weakness of the SAF; the pore pressure in such distributions is less than the least principal stress at every point, so there is no hydraulic fracturing, even though the pressure in the fault zone may be greater than the least principal stress in the nearby crust. Such pore pressure distributions are shown to result from the following assumptions: (1) there is a supply of fluids near the ductile roots of crustal fault zones, where pore pressure must be nearly lithostatic; (2) active fault zones are far more permeable than the adjoining rock of the middle crust; and (3) fault permeability is a rapidly diminishing function of effective normal stress. Evidence in support of these assumptions is discussed. The resulting pore pressure distributions adjust significantly from hydrostatic, such that the effective normal stress, and hence also the brittle frictional strength, becomes approximately independent of depth along the fault zone. These assumptions also predict the possibility of diffusive surges of pore pressure that propagate upward along a fault in a slow wavelike manner.
We consider rupture initiation and instability on a displacement-weakening interface. It is assumed to follow a power-law relation between a component of d
