A novel inhibitory motif against aspartic proteases identified in thyropins

Jaroslav Srp, Petr Pachl, Lisa-Maria Weinhold, Daniela Polatová, Marina Bakardjieva, Martin Horn, Michael Mareš

Institute of Organic Chemistry and Biochemistry, CAS, Flemingovo n. 2, Prague, Czech Republic

Equistatin from sea anemone belongs to the thyropin (thyroglobulin type-1-like) protease inhibitor family. The equistatin domain 2 (Eqd2) is a potent inhibitor of aspartic proteases of cathepsin D type from the pepsin family. We prepared and crystallized a complex of recombinant Eqd2 with a prototype cathepsin D-like protease (CatD). Here we present the crystal structure of the Eqd2-CatD complex solved at 1.7 Å resolution. This revealed the architecture of the reactive site on Eqd2 with a unique inhibitory motif against aspartic proteases that directly targets catalytic diad residues.