Structure of a Kunitz-type potato cathepsin D inhibitor

• Published in: Journal of structural biology 2015-12, Vol.192 (3), p.554-560
• Main Authors: Guo, Jingxu, Erskine, Peter T., Coker, Alun R., Wood, Steve P., Cooper, Jonathan B.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Catalytic Domain - physiology; Cathepsin D - antagonists & inhibitors; Crystallography, X-Ray; Docking; Humans; Kunitz-type protease inhibitor; Models, Molecular; Molecular Docking Simulation; Molecular Sequence Data; Peptides - metabolism; Plant Proteins - metabolism; Plant Proteins - ultrastructure; Potato cathepsin D inhibitor; Protein X-ray structure; Reactive-site loop; Sequence Alignment; Solanum tuberosum - metabolism; Trypsin - metabolism; Trypsin Inhibitors - metabolism
• ISSN: 1047-8477; 1095-8657
• DOI: 10.1016/j.jsb.2015.10.020

Potato cathepsin D inhibitor (PDI) is a glycoprotein of 188 amino acids which can inhibit both the aspartic protease cathepsin D and the serine protease trypsin. Here we report the first X-ray structure of PDI at a resolution of 2.1Å showing that PDI adopts a β-trefoil fold, which is typical of the Kunitz-family protease inhibitors, with the inhibitory loops protruding from the core. Possible reactive-site loops including one involving a unique disulphide and another involving a protruding 310 helix are identified and docking studies indicate the mode of action of this unusual bi-functional inhibitor.