Crystal structures of two protease
inhibitors from tick saliva
P. Řezáčová1,2, J. Brynda1,2, Zuzana Kovářová1, Jiří Salát3, Jindřich Chmelař3, Michal Mareš1
1Institute of Organic Chemistry and
Biochemistry,
2 Institute of Molecular Genetics Academy of Sciences of the Czech
Republic, v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic
3Institute of
Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic,
Branišovská 31, 37005 České Budějovice, Czech Republic
rezacova@uochb.cas.cz
The saliva of ticks is a rich source of
various protease inhibitors which help the blood-feeding parasite to overcome
the defense of host immune system. Two proteins
Protein IRS-2 belongs to the serpin family
of protease inhibitors. It is produced in the salivary glands of the hard tick Ixodes ricinus and exhibits an activity
in suppressing the adaptive host immune response [1]. Recombinant protein was
prepared by heterologous expression in bacterial system and the crystal
structure was determined at resolution of 1.8 Å [2]. IRS-2 adopt a
typical serpin fold composed of 3 large b-sheets and 9 a-helixes
Protein OmC-2 belonging to cystatin family
of protease inhibitors was identified in the salive of the soft tick Ornithodorus moubata by proteomic
approach. The inhibitory activity of OmC2 toward broad-range of human
peptidases was confirmed as well as its immunomodulatory activity in vivo. OmC2 represents a promising
target for the development of anti-tick vaccine. Crystal structure of
recombinant OmC2 determined at resolution of 2.45 Å was used to explain
the structure-inhibitory activity relationship [3]. OmC2 adopts a typical
cystatin fold characterized by five-stranded twisted antiparallel b-sheet wrapping around a central helix
Figure 1. A. Crystal
structure of serpin IRS-2 from hard tick Ixodes
ricinus
1. 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. Blood 117
2. Kovarova,
Z.; Chmelar, J.; Sanda, M.; Brynda, J.; Mares, M.; Rezacova, P. Acta Crystallogr Sect F Struct Biol Cryst
Commun 66
3. Salat,
J.; Paesen, G. C.; Rezacova, P.; Kotsyfakis, M.; Kovarova, Z.; Sanda, M.;
Majtan, J.; Grunclova, L.; Horka, H.; Andersen, J. F.; Brynda, J.; Horn, M.;
Nunn, M. A.; Kopacek, P.; Kopecky, J.; Mares, M. Biochem J 429