Structure and mechanism of heparin and heparan sulfate degrading heparinase II from F. heparinum
Miroslaw Cygler, David Shaya, Yunge Li, James Myette

Enzymes employ two different mechanisms to degrade glycosaminoglycans. Hydrolases break the glycosidic bond between sugars by water addition and their enzymatic mechanism is well understood. Lyases cleave the bond on the non-reducing end of a uronic acid and employ an eliminative mechanism which involves the neutralization of the acidic group of the uronic acid residue followed by proton abstraction at C-5 position of the acid and -elimination of the 4-O-glycosidic bond. Heparinase II depolymerizes heparin and heparan-sulfate glycosaminoglycan affording unsaturated oligosaccharide products via an eliminative mechanism. We have determined the structure of the first heparinase, that of heparinase II from Pedobacter heparinus (formerly Flavobacterium heparinum). The structure of the enzyme complexed with disaccharide reaction products allowed us to localize the substrate binding site and identify putative catalytic residues. Comparison with chondroitin and alginate lyases will be presented.