Differences in PAR-2 activating potential by king crab (Paralithodes camtschaticus), salmon (Salmo salar), and bovine (Bos taurus) trypsin

BMC Research Notes

Berit E Bang¹  Ole-Morten Seternes²  Ingebrigt Sylte¹  Kurt Kristiansen¹  Anett K Larsen¹ 

[1]Medical Pharmacology and Toxicology, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

[2]Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

关键词: Electrostatic interaction;    Protease-activated receptor-2;    Molecular modelling;    King crab trypsin;   

Others  :  1142119
DOI  :  10.1186/1756-0500-6-281

 received in 2013-02-21, accepted in 2013-07-03,  发布年份 2013

【 摘 要 】

Background

Salmon trypsin is shown to increase secretion of the pro-inflammatory cytokine interleukin (IL)-8 from human airway epithelial cells through activation of PAR-2. Secretion of IL-8 induced by king crab trypsin is observed in a different concentration range compared to salmon trypsin, and seems to be only partially related to PAR-2 activation. This report aim to identify differences in the molecular structure of king crab trypsin (Paralithodes camtschaticus) compared to salmon (Salmo salar) and bovine trypsin (Bos taurus) that might influence the ability to activate protease-activated receptor-2 (PAR-2).

Results

During purification king crab trypsin displayed stronger binding capacity to the anionic column used in fast protein liquid chromatography compared to fish trypsins, and was identified as a slightly bigger molecule. Measurements of enzymatic activity yielded no obvious differences between the trypsins tested. Molecular modelling showed that king crab trypsin has a large area with strong negative electrostatic potential compared to the smaller negative areas in bovine and salmon trypsins. Bovine and salmon trypsins also displayed areas with strong positive electrostatic potential, a feature lacking in the king crab trypsin. Furthermore we have identified 3 divergent positions (Asp¹⁹⁶, Arg²⁴⁴, and Tyr²⁴⁷) located near the substrate binding pocket of king crab trypsin that might affect the binding and cleavage of PAR-2.

Conclusion

These preliminary results indicate that electrostatic interactions could be of importance in binding, cleavage and subsequent activation of PAR-2.

【 授权许可】

   
2013 Larsen et al.; licensee BioMed Central Ltd.

【 图 表 】

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