Sialidase gene structures

Since the tertiary structure of bacterial sialidases is similar to that found in viral sialidases (e.g. refs. [756,792-794], for a review see ref. [246]) and residues of the Asp-box have also been found, viral and bacterial sialidases can be considered to belong to one enzyme family. The few mammalian sialidases sequenced so far, i.e. from rat muscle [774] or hamster ovary cells [775], as well as trypanosomal sialidases (see in section 9.2.3), also show many structural features in common with viral and bacterial sialidases and are correspondingly members of this family. A DNA sequence of human origin showing features similar to microbial sialidase genes is also known [795]. However,... 

Presently, several laboratories are intensively studying the gene structures of try-panosomal tra j-sialidases, in order to understand the differences between this unique enzyme and conventional sialidases. In accordance with the latter sialidases, the trans-sialidase genes of T. cruzi [768,776,814-818] also contain several Asp-boxes, first found in bacterial sialidases (see section 9.2.2 and Table 18). In addition, the T. cruzi trans-... 

Similarly to NEUl, NEU2 contains multiple Asp-box motifs of which one is less conserved (residues 247-254) and two are eanonical Asp-boxes (residues 129-136 and 199-206). Stmcturally, Asp boxes show a (3-hairpin structure stabilized by a water molecule at the center of three eonserved residues of serine, aspartate, and tryptophan, and are found in topologically equivalent positions in all members of the sialidase gene family. Interestingly, Asp-boxes are found in protein families having different sequences and three-dimensional structures, sueh as bacterial ribonucleases, reelin,... 

T. cruzi is an exceptional system for glycobiology studies and the most unusual structures have been identified. From the medical point of view, the mucin and trans-sialidase families, which constitute 15% of all predicted genes, are involved in the infection process. 

In the first primary structures of microbial sialidases, obtained by cloning and sequencing of the respective genes from Clostridium perfringens [769], Vibrio cholerae [770], Clostridium sordellii [77 ] and Salmonella typhimurium [772], an amino acid sequence motif was detected, which is repeated four-fold in each protein S-X-D-X-G-X-T-W [773]. This motif, named the Asp-box, was found in all 16 sialidases of animals, trypanosomes, and bacteria, which have so far been sequenced (see refs. [660,768] and Table 18). In viral sialidases, however, the motif was rarely detectable (e.g. only the sialidase from N9 influenza A virus strain exhibits the complete motif [786] and has probably undergone mutational alterations). 

---