Functional and structural characterization of a heparanase

November 2nd, 2015 by Lisa Bohlmann

Nature Chemical Biology 11, 955 (2015). doi:10.1038/nchembio.1956

Authors: Lisa Bohlmann, Gregory D Tredwell, Xing Yu, Chih-Wei Chang, Thomas Haselhorst, Moritz Winger, Jeffrey C Dyason, Robin J Thomson, Joe Tiralongo, Ifor R Beacham, Helen Blanchard & Mark von Itzstein

We report the structural and functional characterization of a novel heparanase (BpHep) from the invasive pathogenic bacterium Burkholderia pseudomallei (Bp), showing ∼24% sequence identity with human heparanase (hHep). Site-directed mutagenesis studies confirmed the active site resi-dues 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.