Catalytic Mechanism of Endosialidase

As discussed in the previous section, exosialidases and endosialidases have different active site topologies. Although three residues have been identified to be highly 

Tyr-325 (b). After release of the reducing end moiety (ROH, c) the initial state of the active site is regenerated by proton transfer via a water chain ([H20] , d) and re-binding of polysiahc acid. In total, the stmctural data allow the conclusion that the endosialidase mechanism is an SNl-type reaction, i.e., the sialic acid stereochemistry is directly inverted into the p-anomer [106]. By contrast, exosialidases form a covalently bound intermediate which is released by a water molecule thus the a2,8-linked sialic acid residue is released as a-anomer tmderlying the mutarotation towards the energetically favored p-conformation. However, no crystal structure of a non-cleavable substrate is available as yet, which would allow an unambiguous elucidation of the endosialidase mechanism [106]. 

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