Chemical shift assignments and secondary structure of the surrogate domain for drug discovery studies of human heparanase

• Published in: Biomolecular NMR assignments 2015-04, Vol.9 (1), p.15-19
• Main Authors: Mosulén, Silvia, Pineda-Lucena, Antonio, Carbajo, Rodrigo J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biochemistry; Biological and Medical Physics; Biophysics; Cancer; Drug Discovery; Enzyme Inhibitors - pharmacology; Glucuronidase - antagonists & inhibitors; Glucuronidase - chemistry; Heparan sulfate; Humans; Matrix; Molecular Sequence Data; NMR; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Physics; Physics and Astronomy; Polymer Sciences; Protein Structure, Secondary; Protein Structure, Tertiary
• ISSN: 1874-2718; 1874-270X
• DOI: 10.1007/s12104-013-9536-9

Heparanase is an endoglycosidase that specifically degrades heparan sulfate, one of the main components of the extracellular matrix. Heparanase is implicated in cancer processes such as tumour formation, angiogenesis and metastasis, making it a very attractive target in drug discovery. Its active form is a heterodimer constituted by a 45 kDa glycosylated subunit (Lys158–Ile543) non-covalently bound to a smaller 8 kDa polypeptide (Gln36–Glu109). Residues Glu225 and Glu343 are critical in its catalytic mechanism and two heparan sulfate binding sites (Lys158–Asp171 and Gln270–Lys280) have been identified in the enzyme. Here we report the 1 H, 13 C and 15 N chemical shift assignments, secondary structure and chemical shift deviations from random coil of the domain of human heparanase comprising residues Lys158–Lys417, a construct that has been validated as surrogate of the full length protein in the search of novel inhibitors for this enzyme.