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 n m ) and three parasite cysteine proteases ( CP 14019, CP 16160 and CP 16779, K i ≈ 0.9–5.8 n m ), but a weaker inhibitor of human cathepsin B ( K i ≈ 79.9 n m ). 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.