Crystal structure of calcium bound domain VI of calpain at 1.9 Å resolution and its role in enzyme assembly, regulation, and inhibitor binding

Academic Article

Abstract

  • The three dimensional structure of calcium-bound domain VI of porcine calpain has been determined to 1.9 Å resolution. The crystal structure reveals five EF-hands, one more than previously suggested. There are two EF- hand pairs, one pair (EF1-EF2) displays an 'open' conformation and the other (EF3-EF4) a 'closed' conformation. Unusually, a calcium atom is found at the C-terminal end of the calcium binding loop of EF4. With two additional residues in the calcium binding loop, the fifth EF-hand (EF5) is in a 'closed' conformation. EF5 pairs up with the corresponding fifth EF-hand of a non-crystallographically related molecule. Considering the EF5's role in a homodimer formation of domain VI, we suggest a model for the assembly of heterodimeric calpain. The crystal structure of a Ca2+ bound domain VI- inhibitor (PD150606) complex has been refined to 2.1 Å resolution. A possible mode for calpain inhibition is discussed.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Lin GD; Chattopadhyay D; Maki M; Wang KKW; Carson M; Jin L; Yuen PW; Takano E; Hatanaka M; DeLucas LJ
  • Start Page

  • 539
  • End Page

  • 547
  • Volume

  • 4
  • Issue

  • 7