Testican-1, a secreted proteoglycan enriched in brain, has a single thyropin domain that is highly homologous to domains previously shown to inhibit cysteine proteases. We demonstrate that purified recombinant human testican-1 is a strong competitive inhibitor of the lysosomal cysteine pro-tease, cathepsin L,withaKiof , but it does not inhibit the structurally related lysosomal cysteine protease cathep-sin B. Testican-1 inhibition of cathepsin L is independent of its chondroitin sulfate chains and is effective at both pH neutral pH, testican-1also stabilizes cathepsin L, slowing pH-induced denaturation and allowing the protease to remain active longer, although the rate of proteolysis is reduced. .
