title: The Intrinsic Pepsin Resistance of Interleukin-8 Can Be Explained from a Combined Bioinformatical and Experimental Approach.
abstract: Interleukin-8 (IL-8, CXCL8) is a neutrophil chemotactic factor belonging to the family of chemokines. IL-8 was shown to resist pepsin cleavage displaying its high resistance to this protease. However, the molecular mechanisms underlying this resistance are not fully understood. Using our in-house database containing the data on three-dimensional arrangements of secondary structure elements from the whole Protein Data Bank, we found a striking structural similarity between IL-8 and pepsin inhibitor-3. Such similarity could play a key role in understanding IL-8 resistance to the protease pepsin. To support this hypothesis, we applied pepsin assays confirming that intact IL-8 is not degraded by pepsin in comparison to IL-8 in a denaturated state. Applying1H-15N Heteronuclear Single Quantum Coherence NMR measurements, we determined the putative regions at IL-8 that are potentially responsible for interactions with the pepsin. The results obtained in this work contribute to the understanding of the resistance of IL-8 to pepsin proteolysis in terms of its structural properties.
authors.forename: Gerd
authors.initials: G
authors.lastname: Anders
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hassiepen
authors.forename: Stephan
authors.initials: S
authors.lastname: Theisgen
authors.forename: Stephan
authors.initials: S
authors.lastname: Heymann
authors.forename: Lionel
authors.initials: L
authors.lastname: Muller
authors.forename: Tania
authors.initials: T
authors.lastname: Panigada
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Samsonov
mesh_terms: D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D016209:Interleukin-8 / Q000737:chemistry* / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010434:Pepsin A / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D016209:Interleukin-8; D010434:Pepsin A