title: The solution structure of the kallikrein-related peptidases inhibitor SPINK6.
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.
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Olshausenstr. 40, 24098 Kiel, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Olshausenstr. 40, 24098 Kiel, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Spudy
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Olshausenstr. 40, 24098 Kiel, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Kerkow
authors.affiliation: Otto Diels Institute of Organic Chemistry, Christian-Albrechts-University, Olshausenstr. 40, 24098 Kiel, Germany.
authors.forename: Frank D
authors.initials: FD
authors.lastname: Sönnichsen
authors.affiliation: Bijvoet Center for Biomolecular Research, Faculty of Science - Chemistry, Utrecht University, Utrecht 3584 CH, The Netherlands.
authors.forename: Li
authors.initials: L
authors.lastname: Xue
authors.affiliation: Bijvoet Center for Biomolecular Research, Faculty of Science - Chemistry, Utrecht University, Utrecht 3584 CH, The Netherlands.
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Goettig
authors.affiliation: Klinische Forschergruppe der Frauenklinik, Klinikum rechts der Isar, TU München, Munich, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Magdolen
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Meyer-Hoffert
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Olshausenstr. 40, 24098 Kiel, Germany. Electronic address: jgroetzinger@biochem.uni-kiel.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D004789:Enzyme Activation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D053491:Proteinase Inhibitory Proteins, Secretory / Q000737:chemistry* / Q000648:ultrastructure*; D020539:Sequence Analysis, Protein / Q000379:methods; D000074162:Serine Peptidase Inhibitors, Kazal Type
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; C553928:SPINK6 protein, human; D000074162:Serine Peptidase Inhibitors, Kazal Type
keywords: KLK4; Kallikrein-related peptidase 4; Model protease – inhibitor complex; Nuclear magnetic resonance; SPINK6; Structure
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