3NDA

Crystal structure of serpin from tick Ixodes ricinus

3NDA の概要

• エントリーDOI: 10.2210/pdb3nda/pdb
• 分子名称: Serpin-2, PENTAETHYLENE GLYCOL (3 entities in total)
• 機能のキーワード: serpin, vaccination target, tick, hydrolase inhibitor
• 由来する生物種: Ixodes ricinus (Sheep tick)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84533.72

構造登録者

Rezacova, P.,Kovarova, Z.,Chmelar, J.,Mares, M. (登録日: 2010-06-07, 公開日: 2010-10-27, 最終更新日: 2023-11-01)

主引用文献

Chmelar, J.,Oliveira, C.J.,Rezacova, P.,Francischetti, I.M.,Kovarova, Z.,Pejler, G.,Kopacek, P.,Ribeiro, J.M.,Mares, M.,Kopecky, J.,Kotsyfakis, M.
A tick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation.
Blood, 117:736-744, 2011

PubMed Abstract: Platelet aggregation and acute inflammation are key processes in vertebrate defense to a skin injury. Recent studies uncovered the mediation of 2 serine proteases, cathepsin G and chymase, in both mechanisms. Working with a mouse model of acute inflammation, we revealed that an exogenous salivary protein of Ixodes ricinus, the vector of Lyme disease pathogens in Europe, extensively inhibits edema formation and influx of neutrophils in the inflamed tissue. We named this tick salivary gland secreted effector as I ricinus serpin-2 (IRS-2), and we show that it primarily inhibits cathepsin G and chymase, while in higher molar excess, it affects thrombin activity as well. The inhibitory specificity was explained using the crystal structure, determined at a resolution of 1.8 Å. Moreover, we disclosed the ability of IRS-2 to inhibit cathepsin G-induced and thrombin-induced platelet aggregation. For the first time, an ectoparasite protein is shown to exhibit such pharmacological effects and target specificity. The stringent specificity and biological activities of IRS-2 combined with the knowledge of its structure can be the basis for the development of future pharmaceutical applications.

PubMed: 20940421
DOI: 10.1182/blood-2010-06-293241

実験手法

X-RAY DIFFRACTION (1.8 Å)