The solution structure of the kallikrein-related peptidases inhibitor SPINK6

Autor: 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, Sub NMR Spectroscopy, NMR Spectroscopy
Přispěvatelé: Sub NMR Spectroscopy, NMR Spectroscopy
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Models
Molecular
Magnetic Resonance Spectroscopy
Protein Conformation
KLK4
Molecular Sequence Data
Biophysics
Proteinase Inhibitory Proteins
Secretory
Plasma protein binding
Biochemistry
Article
Nuclear magnetic resonance
Desquamation
03 medical and health sciences
Enzyme activator
0302 clinical medicine
Protein structure
Sequence Analysis
Protein
SPINK6
Taverne
medicine
Humans
Computer Simulation
Amino Acid Sequence
Binding site
Molecular Biology
Serine protease
Binding Sites
biology
Kallikrein-related peptidase 4
integumentary system
Serine Peptidase Inhibitors
Kazal Type
Structure
Cell Biology
Kallikrein
Enzyme Activation
030104 developmental biology
Models
Chemical
030220 oncology & carcinogenesis
biology.protein
medicine.symptom
Model protease – inhibitor complex
Protein Binding
Zdroj: Biochemical and Biophysical Research Communications, 471(1), 103. Academic Press Inc.
ISSN: 0006-291X
Popis: 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.
Databáze: OpenAIRE
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