The solution structure of the kallikrein-related peptidases inhibitor SPINK6

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 ser...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biochemical and biophysical research communications 2016-02, Vol.471 (1), p.103-108
Hauptverfasser: Jung, Sascha, Fischer, Jan, Spudy, Björn, Kerkow, Tim, Sönnichsen, Frank D., Xue, Li, Bonvin, Alexandre M.J.J., Goettig, Peter, Magdolen, Viktor, Meyer-Hoffert, Ulf, Grötzinger, Joachim
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. •Solution structure SPINK6 reveals an flexible N-terminus.•A model of the SPINK6 kallikrein 4 complex shows alternative binding modes.•Serine protease Kazal type inhibitor.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2016.01.172