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

Peptides. 2011 Jun;32(6):1187-92. doi: 10.1016/j.peptides.2011.03.009. Epub 2011 Mar 23.

Abstract

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 1nM, KLK4 with K(i)=27.3nM, KLK6 with K(i)=140nM, caspase-14 with a K(i) approximating 1μM and no activity against KLK1, KLK3 and KLK11. Taken together, SPINK6 is a potent inhibitor of distinct KLKs members.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Caspase 14 / metabolism
  • Caspase Inhibitors*
  • Chromogenic Compounds / metabolism
  • Enzyme Activation
  • Humans
  • Kallikreins / antagonists & inhibitors*
  • Kallikreins / metabolism
  • Kinetics
  • Molecular Sequence Data
  • Proteinase Inhibitory Proteins, Secretory / genetics
  • Proteinase Inhibitory Proteins, Secretory / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Serine Peptidase Inhibitors, Kazal Type
  • Serine Proteinase Inhibitors / genetics
  • Serine Proteinase Inhibitors / metabolism*
  • Skin / metabolism*
  • Solutions
  • Spectrophotometry
  • Substrate Specificity

Substances

  • Caspase Inhibitors
  • Chromogenic Compounds
  • Proteinase Inhibitory Proteins, Secretory
  • Recombinant Proteins
  • SPINK6 protein, human
  • Serine Peptidase Inhibitors, Kazal Type
  • Serine Proteinase Inhibitors
  • Solutions
  • Kallikreins
  • Caspase 14