Structure of a Kunitz-type potato cathepsin D inhibitor

J Struct Biol. 2015 Dec;192(3):554-560. doi: 10.1016/j.jsb.2015.10.020. Epub 2015 Nov 2.

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.

Keywords: Docking; Kunitz-type protease inhibitor; Potato cathepsin D inhibitor; Protein X-ray structure; Reactive-site loop.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain / physiology*
  • Cathepsin D / antagonists & inhibitors*
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Sequence Data
  • Peptides / metabolism
  • Plant Proteins / metabolism
  • Plant Proteins / ultrastructure*
  • Sequence Alignment
  • Solanum tuberosum / metabolism
  • Trypsin / metabolism
  • Trypsin Inhibitors / metabolism

Substances

  • Kunitz-type protease inhibitor, plant
  • Peptides
  • Plant Proteins
  • Trypsin Inhibitors
  • CDI protein, Solanum tuberosum
  • Trypsin
  • Cathepsin D

Associated data

  • PDB/5DZU