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  • The EMBO Journal (1999) 18, 3947 - 3955
  • doi:10.1093/emboj/18.14.3947

Crystal structure of plant aspartic proteinase prophytepsin: inactivation and vacuolar targeting

Jukka Kervinen1,2, Gregory J. Tobin3, Júlia Costa4, David S. Waugh5, Alexander Wlodawer1 and Alexander Zdanov1

  1. Protein Structure Section, Frederick, MD 21702, USA
  2. Present address: Fox Chase Cancer Center, Institute for Cancer Research, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
  3. Laboratory of Cell and Molecular Structure- SAIC, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA
  4. Instituto de Biologia Experimental e Tecnológica/Instituto de Tecnologia Química e Biológica, 2780 Oeiras, Portugal
  5. Protein Engineering Group, Macromolecular Structure Laboratory, ABL-Basic Research Program, Frederick, MD 21702, USA

Correspondence to:

Alexander Zdanov, E-mail: zdanov@ncifcrf.gov

Received 26 April 1999; Accepted 26 May 1999; Revised 26 May 1999

We determined at 2.3 Å resolution the crystal structure of prophytepsin, a zymogen of a barley vacuolar aspartic proteinase. In addition to the classical pepsin-like bilobal main body of phytepsin, we also traced most of the propeptide, as well as an independent plant-specific domain, never before described in structural terms. The structure revealed that, in addition to the propeptide, 13 N-terminal residues of the mature phytepsin are essential for inactivation of the enzyme. Comparison of the plant-specific domain with NK-lysin indicates that these two saposin-like structures are closely related, suggesting that all saposins and saposin-like domains share a common topology. Structural analysis of prophytepsin led to the identification of a putative membrane receptor-binding site involved in Golgi-mediated transport to vacuoles.

  • Keywords:

    • aspartic proteinases,
    • phytepsin,
    • saposin-like domain,
    • transport to vacuoles,
    • zymogen structure