Giardia intestinalis cystatin is a potent inhibitor of papain, parasite cysteine proteases and, to a lesser extent, human cathepsin B.

Cystatins are important regulators of papain-like cysteine proteases. In the protozoan parasite Giardia intestinalis, papain-like cysteine proteases play an essential role in the parasite's biology and pathogenicity. Here, we characterized a cysteine protease inhibitor of G. intestinalis that belongs to type-I-cystatins. The parasite cystatin is shown to be a strong inhibitor of papain (K_i ≈ 0.3 nm) and three parasite cysteine proteases (CP14019, CP16160 and CP16779, K_i ≈ 0.9-5.8 nm), but a weaker inhibitor of human cathepsin B (K_i ≈ 79.9 nm). The protein localizes mainly in the cytoplasm. Together, these data suggest that cystatin of G. intestinalis plays a role in the regulation of cysteine protease activities in the parasite and, possibly, in the interaction with the host.