The solution structure of the kallikrein-related peptidases inhibitor SPINK6

Biochem Biophys Res Commun. 2016 Feb 26;471(1):103-8. doi: 10.1016/j.bbrc.2016.01.172. Epub 2016 Jan 30.

Abstract

Kallikrein-related peptidases (KLKs) are crucial for epidermal barrier function and are involved in the proteolytic regulation of the desquamation process. Elevated KLK levels were reported in atopic dermatitis. In skin, the proteolytic activity of KLKs is regulated by specific inhibitors of the serine protease inhibitor of Kazal-type (SPINK) family. SPINK6 was shown to be expressed in human stratum corneum and is able to inhibit several KLKs such as KLK4, -5, -12, -13 and -14. In order to understand the structural traits of the specific inhibition we solved the structure of SPINK6 in solution by NMR-spectroscopy and studied its interaction with KLKs. Thereby, beside the conserved binding mode, we identified an alternate binding mode which has so far not been observed for SPINK inhibitors.

Keywords: KLK4; Kallikrein-related peptidase 4; Model protease – inhibitor complex; Nuclear magnetic resonance; SPINK6; Structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Computer Simulation
  • Enzyme Activation
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Models, Chemical*
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Proteinase Inhibitory Proteins, Secretory / chemistry*
  • Proteinase Inhibitory Proteins, Secretory / ultrastructure*
  • Sequence Analysis, Protein / methods
  • Serine Peptidase Inhibitors, Kazal Type

Substances

  • Proteinase Inhibitory Proteins, Secretory
  • SPINK6 protein, human
  • Serine Peptidase Inhibitors, Kazal Type