title: Exploring bacterial heparinase II activities with defined substrates.
abstract: Bacterial heparinases that cleave heparan sulfate (HS) and heparin are widely used to generate low-molecular-weight heparins (LMWHs) and to structurally and functionally characterise heparin and HS biomolecules. We provide novel insights into the substrate specificity of heparinase II from two different bacteria: Pedobacter heparinus (formerly Flavobacterium heparinum) and Bacteroides eggerthii. The activity towards various well-defined HS oligosaccharides was investigated by (1) H NMR spectroscopy; this revealed distinct specificities for the two heparinases. Heparinase II from P. heparinus appears to be more active and displays a broader substrate specificity than B. eggerthii heparinase II. Furthermore, HS di- and tetrasaccharides inhibited B. eggerthii heparinase II activity. A better understanding of heparinase substrate specificity will contribute to the production of homogenous LMWHs, provide better characterisation of heparin and HS and assist therapeutic applications.
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland, 4222 (Australia).
authors.forename: Lisa
authors.initials: L
authors.lastname: Bohlmann
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland, 4222 (Australia).
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland, 4222 (Australia).
authors.forename: Ifor
authors.initials: I
authors.lastname: Beacham
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland, 4222 (Australia). m.vonitzstein@griffith.edu.au.
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
mesh_terms: D000991:Antithrombins / Q000378:metabolism; D001438:Bacteroidaceae / Q000201:enzymology*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism; D060485:Pedobacter / Q000201:enzymology*; D011133:Polysaccharide-Lyases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000991:Antithrombins; D004791:Enzyme Inhibitors; D006497:Heparan Sulfate; D011133:Polysaccharide-Lyases; C114663:heparinase II
keywords: enzyme catalysis; heparan sulfate; heparin; heparinase; natural products; substrate specificity