I. Francischetti, A. Sá-nunes, B. Mans, I. Santos, and J. Ribeiro, The role of saliva in tick feeding, Frontiers in Bioscience, vol.Volume, issue.14, pp.2051-2088, 2009.
DOI : 10.2741/3363

C. Maritz-olivier, C. Stutzer, F. Jongejan, A. Neitz, and A. Gaspar, Tick anti-hemostatics: targets for future vaccines and therapeutics, Trends in Parasitology, vol.23, issue.9, pp.397-407, 2007.
DOI : 10.1016/j.pt.2007.07.005

F. Jongejan and G. Uilenberg, The global importance of ticks, Parasitology, vol.96, issue.07, pp.3-14, 2004.
DOI : 10.1016/S0169-4758(99)01472-6

J. Valenzuela, Exploring tick saliva: from biochemistry to ???sialomes??? and functional genomics, Parasitology, vol.129, issue.7, pp.83-94, 2004.
DOI : 10.1017/S0031182004005189

P. Nuttall and M. Labuda, Tick???host interactions: saliva-activated transmission, Parasitology, vol.129, issue.7, pp.177-189, 2004.
DOI : 10.1017/S0031182004005633

S. Iwanaga, M. Okada, H. Isawa, A. Morita, and M. Yuda, Identification and characterization of novel salivary thrombin inhibitors from the ixodidae tick, Haemaphysalis longicornis, European Journal of Biochemistry, vol.85, issue.9, pp.1926-1934, 2003.
DOI : 10.1016/S0002-9149(98)00660-2

C. Nakajima, I. Da-silva-vaz-jr, S. Imamura, S. Konnai, and K. Ohashi, Random Sequencing of cDNA Library Derived from Partially-Fed Adult Female Haemaphysalis longicornis Salivary Gland, Journal of Veterinary Medical Science, vol.67, issue.11, pp.1127-1131, 2005.
DOI : 10.1292/jvms.67.1127

N. Rawlings, A. Barrett, and A. Bateman, MEROPS: the database of proteolytic enzymes, their substrates and inhibitors, Nucleic Acids Research, vol.40, issue.D1, pp.343-350, 2012.
DOI : 10.1093/nar/gkr987

D. Zhang, M. Cupp, and E. Cupp, Thrombostasin: purification, molecular cloning and expression of a novel anti-thrombin protein from horn fly saliva, Insect Biochemistry and Molecular Biology, vol.32, issue.3, pp.321-330, 2002.
DOI : 10.1016/S0965-1748(01)00093-5

M. Cappello, S. Li, X. Chen, C. Li, and L. Harrison, Tsetse thrombin inhibitor: Bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans, Proceedings of the National Academy of Sciences, vol.9, issue.1, pp.14290-14295, 1998.
DOI : 10.1126/science.2374926

C. Nakajima, S. Imamura, S. Konnai, S. Yamada, and H. Nishikado, A Novel Gene Encoding a Thrombin Inhibitory Protein in a cDNA Library from Haemaphysalis longicornis Salivary Gland, Journal of Veterinary Medical Science, vol.68, issue.5, pp.447-452, 2006.
DOI : 10.1292/jvms.68.447

C. Koh, M. Kazimirova, A. Trimnell, P. Takac, and M. Labuda, Variegin, a Novel Fast and Tight Binding Thrombin Inhibitor from the Tropical Bont Tick, Journal of Biological Chemistry, vol.267, issue.40, pp.29101-29113, 2007.
DOI : 10.1111/j.1538-7836.2005.01456.x

A. Figueiredo, D. De-sanctis, R. Gutiérrez-gallego, T. Cereija, and S. Macedo-ribeiro, Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector, Proceedings of the National Academy of Sciences, vol.42, issue.9, pp.3649-3658, 2012.
DOI : 10.1016/j.ibmb.2012.04.008

C. Koh, S. Kumar, M. Kazimirova, P. Nuttall, and U. Radhakrishnan, Crystal Structure of Thrombin in Complex with S-Variegin: Insights of a Novel Mechanism of Inhibition and Design of Tunable Thrombin Inhibitors, PLoS ONE, vol.149, issue.Pt 3, p.26367, 2011.
DOI : 10.1371/journal.pone.0026367.s022

C. Koh and R. Kini, Molecular diversity of anticoagulants from haematophagous animals, Thrombosis and Haemostasis, vol.102, pp.437-453, 2009.
DOI : 10.1160/TH09-04-0221
URL : https://www.schattauer.de/index.php?id=5236&mid=11726

G. Bertani, Studies on lysogenesis. I. The mode of phage liberation by lysogenic Escherichia coli, J Bacteriol, vol.62, pp.293-300, 1951.

L. Whitmore and B. Wallace, Protein secondary structure analyses from circular dichroism spectroscopy: Methods and reference databases, Biopolymers, vol.332, issue.5, pp.392-400, 2008.
DOI : 10.1155/2005/263649
URL : http://onlinelibrary.wiley.com/doi/10.1002/bip.20853/pdf

C. Jr, T. Shaw, and E. , p-Nitrophenyl-p9-guanidinobenzoate HCl: a new active site titrant for trypsin, Biochem Biophys Res Commun, vol.29, pp.508-514, 1967.

D. De-sanctis, A. Beteva, H. Caserotto, F. Dobias, and J. Gabadinho, ID29: a high-intensity highly automated ESRF beamline for macromolecular crystallography experiments exploiting anomalous scattering, Journal of Synchrotron Radiation, vol.5, issue.3, pp.455-461, 2012.
DOI : 10.1107/S0909049597018785

W. Kabsch, Integration, scaling, space-group assignment and post-refinement, Acta Crystallographica Section D Biological Crystallography, vol.34, issue.2, pp.133-144, 2010.
DOI : 10.1107/S0907444909047374
URL : http://doi.org/10.1107/s0907444909047374

A. Mccoy, R. Grosse-kunstleve, P. Adams, M. Winn, and L. Storoni, crystallographic software, Journal of Applied Crystallography, vol.40, issue.4, pp.658-674, 2007.
DOI : 10.1107/S0021889807021206

A. Figueiredo, C. Clement, M. Philipp, and P. Pereira, Crystallization and preliminary crystallographic characterization of three peptidic inhibitors in complex with ??-thrombin, Acta Crystallographica Section F Structural Biology and Crystallization Communications, vol.67, issue.1, pp.54-58, 2011.
DOI : 10.1107/S1744309110043472

A. Figueiredo, C. Clement, S. Zakia, J. Gingold, and M. Philipp, Rational Design and Characterization of D-Phe-Pro-D-Arg-Derived Direct Thrombin Inhibitors, PLoS ONE, vol.39, issue.3, p.34354, 2012.
DOI : 10.1371/journal.pone.0034354.t006
URL : http://doi.org/10.1371/journal.pone.0034354

P. Emsley and K. Cowtan, : model-building tools for molecular graphics, Acta Crystallographica Section D Biological Crystallography, vol.60, issue.12, pp.2126-2132, 2004.
DOI : 10.1107/S0907444904019158
URL : http://doi.org/10.1107/s0907444904019158

P. Adams, P. Afonine, G. Bunkoczi, V. Chen, and I. Davis, : a comprehensive Python-based system for macromolecular structure solution, Acta Crystallographica Section D Biological Crystallography, vol.64, issue.2, pp.213-221, 2010.
DOI : 10.1107/S0907444909052925
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815670/pdf

J. Timmer, W. Zhu, C. Pop, T. Regan, and S. Snipas, Structural and kinetic determinants of protease substrates, Nature Structural & Molecular Biology, vol.414, issue.10, pp.1101-1108, 2009.
DOI : 10.1016/0968-0004(82)90157-8
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042863

M. Stubbs and W. Bode, A player of many parts: The spotlight falls on thrombin's structure, Thrombosis Research, vol.69, issue.1, pp.1-58, 1993.
DOI : 10.1016/0049-3848(93)90002-6

M. Grutter, J. Priestle, J. Rahuel, H. Grossenbacher, and W. Bode, Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition, EMBO J, vol.9, pp.2361-2365, 1990.

C. Liu, E. Brustad, W. Liu, and P. Schultz, Crystal Structure of a Biosynthetic Sulfo-hirudin Complexed to Thrombin, Journal of the American Chemical Society, vol.129, issue.35, pp.10648-10649, 2007.
DOI : 10.1021/ja0735002

T. Rydel, K. Ravichandran, A. Tulinsky, W. Bode, and R. Huber, The structure of a complex of recombinant hirudin and human alpha-thrombin, Science, vol.249, issue.4966, pp.277-280, 1990.
DOI : 10.1126/science.2374926

M. Corral-rodríguez, P. Bock, E. Hernández-carvajal, R. Gutiérrez-gallego, and P. Fuentes-prior, Structural basis of thrombin-mediated factor V activation: the Glu666-Glu672 sequence is critical for processing at the heavy chain-B domain junction, Blood, vol.117, issue.26, pp.7164-7173, 2011.
DOI : 10.1182/blood-2010-10-315309

P. Gandhi, Z. Chen, D. Cera, and E. , Crystal Structure of Thrombin Bound to the Uncleaved Extracellular Fragment of PAR1, Journal of Biological Chemistry, vol.265, issue.20, pp.15393-15398, 2010.
DOI : 10.1074/jbc.M109.069500

M. Gallwitz, M. Enoksson, M. Thorpe, and L. Hellman, The Extended Cleavage Specificity of Human Thrombin, PLoS ONE, vol.9, issue.2, p.31756, 2012.
DOI : 10.1371/journal.pone.0031756.t006

H. Brandstetter, A. Kühne, W. Bode, R. Huber, V. Der-saal et al., X-ray Structure of Active Site-inhibited Clotting Factor Xa, Journal of Biological Chemistry, vol.206, issue.47, pp.29988-29992, 1996.
DOI : 10.1016/0022-2836(74)90163-6

H. Hsu, K. Tsai, Y. Sun, H. Chang, and Y. Huang, Factor Xa Active Site Substrate Specificity with Substrate Phage Display and Computational Molecular Modeling, Journal of Biological Chemistry, vol.154, issue.18, pp.12343-12353, 2008.
DOI : 10.1021/cr9603744
URL : http://www.jbc.org/content/283/18/12343.full.pdf

K. Padmanabhan, K. Padmanabhan, A. Tulinsky, C. Park, and W. Bode, Structure of Human Des(1-45) Factor Xa at 2??2 ?? Resolution, Journal of Molecular Biology, vol.232, issue.3, pp.947-966, 1993.
DOI : 10.1006/jmbi.1993.1441

J. Rios-steiner, M. Murakami, A. Tulinsky, and R. Arni, Active and Exo-site Inhibition of Human Factor Xa: Structure of des-Gla Factor Xa Inhibited by NAP5, a Potent Nematode Anticoagulant Protein from Ancylostoma caninum, Journal of Molecular Biology, vol.371, issue.3, pp.774-786, 2007.
DOI : 10.1016/j.jmb.2007.05.042

C. Sadasivan and Y. Vc, Interaction of the Factor XIII Activation Peptide with ??-Thrombin, Journal of Biological Chemistry, vol.326, issue.47, pp.36942-36948, 2000.
DOI : 10.1002/prot.340110407

A. Bah, Z. Chen, L. Bush-pelc, F. Mathews, D. Cera et al., Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4, Proceedings of the National Academy of Sciences, vol.12, issue.4, pp.11603-11608, 2007.
DOI : 10.1002/prot.340120407

I. Komáromi, Z. Bagoly, and L. Muszbek, Factor XIII: novel structural and functional aspects, Journal of Thrombosis and Haemostasis, vol.14, issue.1, pp.9-20, 2011.
DOI : 10.1016/0263-7855(96)00018-5

L. Muszbek, V. Yee, and Z. Hevessy, Blood Coagulation Factor XIII, Thrombosis Research, vol.94, issue.5, pp.271-305, 1999.
DOI : 10.1016/S0049-3848(99)00023-7

D. Cleary, T. Trumbo, and M. Maurer, Protease-activated receptor 4-like peptides bind to thrombin through an optimized interaction with the enzyme active site surface, Archives of Biochemistry and Biophysics, vol.403, issue.2, pp.179-188, 2002.
DOI : 10.1016/S0003-9861(02)00220-5

M. Laskowski and I. Kato, Protein Inhibitors of Proteinases, Annual Review of Biochemistry, vol.49, issue.1, pp.593-626, 1980.
DOI : 10.1146/annurev.bi.49.070180.003113

K. Stierand and M. Rarey, Drawing the PDB: Protein???Ligand Complexes in Two Dimensions, ACS Medicinal Chemistry Letters, vol.1, issue.9, pp.540-545, 2010.
DOI : 10.1021/ml100164p