title: Structure of a Kunitz-type potato cathepsin D inhibitor.
abstract: 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 2.1 Å 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.
authors.affiliation: Division of Medicine, UCL, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Jingxu
authors.initials: J
authors.lastname: Guo
authors.affiliation: Division of Medicine, UCL, Gower Street, London WC1E 6BT, United Kingdom; Department of Biological Sciences, Birkbeck, University of London, Malet Street, Bloomsbury, London WC1E 7HX, United Kingdom.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Erskine
authors.affiliation: Division of Medicine, UCL, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Alun R
authors.initials: AR
authors.lastname: Coker
authors.affiliation: Division of Medicine, UCL, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Steve P
authors.initials: SP
authors.lastname: Wood
authors.affiliation: Division of Medicine, UCL, Gower Street, London WC1E 6BT, United Kingdom; Department of Biological Sciences, Birkbeck, University of London, Malet Street, Bloomsbury, London WC1E 7HX, United Kingdom. Electronic address: jon.cooper@ucl.ac.uk.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Cooper
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain / Q000502:physiology*; D002402:Cathepsin D / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D010940:Plant Proteins / Q000378:metabolism / Q000648:ultrastructure*; D016415:Sequence Alignment; D011198:Solanum tuberosum / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000378:metabolism
chemical_list: C053865:Kunitz-type protease inhibitor, plant; D010455:Peptides; D010940:Plant Proteins; D014361:Trypsin Inhibitors; C060481:CDI protein, Solanum tuberosum; D014357:Trypsin; D002402:Cathepsin D
keywords: Docking; Kunitz-type protease inhibitor; Potato cathepsin D inhibitor; Protein X-ray structure; Reactive-site loop