Our group’s efforts in the field
of molecular biology are directed towards establishing
recombinant proteins important in glycobiology and
towards developing enzymatic tools for glycan analysis.
Our enzymology programs consist largely of enzymes
that degrade glycosaminoglycans. These tools have been
incorporated into our broader multidisciplinary strategy
to analyze glycans. Some of these enzymes are themselves
being investigated as therapeutics for human disease.
A major research aim of our laboratory is to clone
and biochemically characterize a series of HSGAG-degrading
enzymes or heparinases. We hope to develop tools for
the study of HSGAGs that will facilitate structure-function
studies in a manner similar to that in which proteases
promoted studies for proteins or restriction enzymes
promoted studies for DNA. The heparinases are lyases
that depolymerize HSGAGs in a sequence-specific fashion.
Three heparinases, heparinases I, II, and III from
the soil bacterium Pedobacter heparinus, have
been isolated and each cleaves HSGAGs at different
Similarly, we have sought recombinant versions of
enzymes that selectively and uniquely depolymerize
chondroitin and dermatan sulfate GAGs, galactosaminoglycans
(GalAGs). Our laboratory is home to the most complete
library of recombinant and engineered depolymerizing
lyases specific for GalAGs in the world.
HSGAG Exo-Enzyme Library
Depolymerizing lyases are useful tools to break a
linear polysaccharide chain into constituent oligosaccharide
fragments, but complete degradation also requires enzyme
activities working at the ends of oligosaccharide chains
and at specific sites within disaccharide units that
can be differentially modified chemically.