| Literature DB >> 26828269 |
Sascha Jung1, Jan Fischer2, Björn Spudy1, Tim Kerkow1, Frank D Sönnichsen3, Li Xue4, Alexandre M J J Bonvin4, Peter Goettig5, Viktor Magdolen6, Ulf Meyer-Hoffert2, Joachim Grötzinger7.
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.Entities:
Keywords: KLK4; Kallikrein-related peptidase 4; Model protease – inhibitor complex; Nuclear magnetic resonance; SPINK6; Structure
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Year: 2016 PMID： 26828269 PMCID： PMC5553623 DOI： 10.1016/j.bbrc.2016.01.172
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575