Inverting family GH156 sialidases define an unusual catalytic motif for glycosidase action

Sialic acids are a family of related sugars that play essential roles in many biological events intimately linked to cellular recognition in both health and disease. Sialidases are therefore orchestrators of cellular biology and important therapeutic targets for viral infection. Here, we sought to define if uncharacterized sialidases would provide distinct paradigms in sialic acid biochemistry. We show that a recently discovered sialidase family, whose first member EnvSia156 was isolated from hot spring metagenomes, defines an unusual structural fold and active centre constellation, not previously described in sialidases. Consistent with an inverting mechanism, EnvSia156 reveals a His/Asp active center in which the His acts as a Bronsted acid and Asp as a Bronsted base in a single-displacement mechanism. A pre-dominantly hydrophobic aglycone site facilitates accommodation of a variety of 2-linked sialosides; a versatility that offers the potential for glycan hydrolysis across a range of biological and technological platforms

Comparison between macrophage activation and enhancement of nonspecific resistance to tumors by mycobacterial immunoadjuvants.

It has repeatedly been observed that various bacterial preparations could increase the host's resistance to tumors. It has also been shown that after nonspecific activation by BCG (bacillus Calmette-Guérin), peritoneal macrophages could inhibit in vitro the growth of neoplastic target cells. In the present study a fraction extracted from Myobacterium smegmatis and referred to as interphase material was tested in view of measuring its ability to activate macrophages in vitro and in vivo. This preparation was previously shown to protect mice against a syngeneic leukemia and to increase the immune response of the guinea pig. Other water-soluble adjuvants devoid of demonstrable antitumor activity in vivo were also assayed. The results argue in favor of a correlation between adjuvant activity and the capacity of activating macrophages. Moreover, interphase material administered in vivo consistently induced stronger and more persistent stimulations of macrophages than the other preparations assayed