Inhibition of kallikrein-related peptidases by the serine protease inhibitor of Kazal-type 6

Kallikrein-related peptidases (KLKs) are a group of serine proteases, expressed in several tissues. Their activity is regulated by inhibitors including members of the serine protease of Kazal-type (SPINK) family. Recently, we discovered that SPINK6 is expressed in human skin and inhibits KLK5, KLK7, KLK14 but not KLK8. In this study we tested whether SPINK6 inhibits other members of the KLK family and caspase-14. Using chromogenic substrates, SPINK6 exhibited inhibitory activity against KLK12 and KLK13 with K-i around 1 nM, KLK4 with K-i = 27.3 nM, KLK6 with K-i = 140 nM, caspase-14 with a K-i approximating 1 mu M and no activity against KLK1, KLK3 and KLK11. Taken together, SPINK6 is a potent inhibitor of distinct KLKs members. (C) 2011 Elsevier Inc. All rights reserved.