A complex of chagasin, a protein inhibitor fromTrypanosoma cruzi, and papain, a classic family C1 cysteine protease, has been crystallized. Kinetic studies revealed that inactivation of papain by chagasin is very fast (kon= ·10 6 m )1 Æs )1 ), and results in the formation of a very tight, reversible complex (Ki =36pm), with similar or better rate and equilib-rium constants than those for cathepsins L and B.