TY - JOUR
T1 - The solution structure of the kallikrein-related peptidases inhibitor SPINK6
AU - Jung, Sascha
AU - Fischer, Jan
AU - Spudy, Björn
AU - Kerkow, Tim
AU - Sönnichsen, Frank D.
AU - Xue, Li
AU - Bonvin, Alexandre M.J.J.
AU - Goettig, Peter
AU - Magdolen, Viktor
AU - Meyer-Hoffert, Ulf
AU - Grötzinger, Joachim
N1 - Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/2/26
Y1 - 2016/2/26
N2 - 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.
AB - 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.
KW - KLK4
KW - Kallikrein-related peptidase 4
KW - Model protease - inhibitor complex
KW - Nuclear magnetic resonance
KW - SPINK6
KW - Structure
UR - http://www.scopus.com/inward/record.url?scp=84958927228&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2016.01.172
DO - 10.1016/j.bbrc.2016.01.172
M3 - Article
C2 - 26828269
AN - SCOPUS:84958927228
SN - 0006-291X
VL - 471
SP - 103
EP - 108
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -