Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, Australia.
Nat Chem Biol. 2015 Dec;11(12):955-7. doi: 10.1038/nchembio.1956. Epub 2015 Nov 2.
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.
我们报告了一种新型肝素酶（BpHep）的结构和功能特征，该酶来自侵袭性病原菌伯克霍尔德菌假单胞菌（Bp），与人类肝素酶（hHep）具有约 24%的序列同一性。定点突变研究证实了活性位点残基对活性是必需的，我们发现 BpHep 对硫酸乙酰肝素具有特异性。最后，我们描述了第一个肝素酶 X 射线晶体结构，为底物识别和抑制剂设计提供了新的见解。
