Functional and structural characterization of a heparanase

We report the structural and functional characterization of a novel heparanase (BpHep) from the invasive pathogenic bacterium Burkholderia pseudomallei (Bp), showing similar to 24% sequence identity with human heparanase (hHep). Site-directed mutagenesis studies confirmed the active site residues essential for activity, and we found that BpHep has specificity for heparan sulfate. Finally, we describe the first heparanase X-ray crystal structure, which provides new insight into both substrate recognition and inhibitor design.