Thrombin Inhibitors from Haematophagous Animals
To facilitate the feeding of blood, hematophagous animals use pharmacologically active molecules to ensure free-flowing of blood at both the feeding site and within the digestion system. A number of these exogenous anticoagulants have been identified and characterized in recent years. Among them, inhibitors of thrombin form the largest group both in terms of number and diversity. To date, more than 30 different exogenous thrombin inhibitors from hematophagous animals, grouped into at least 15 unique structural classes, have been reported in the literature. In this chapter, we discuss five representative classes in detail with insights from their high resolution structures in complex with thrombin.
KeywordsSalt Bridge Hydrophobic Contact Factor Versus Medicinal Leech Soft Tick
This work is supported by academic research grants from National University of Singapore, Singapore.
- Bode, W., Turk, D., Karshikov, A., 1992. The refined 1.9-A X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human α-thrombin: structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationships. Protein Sci. 1, 426–471.PubMedCrossRefGoogle Scholar
- Campos, I.T., Amino, R., Sampaio, C.A., Auerswald, E.A., Friedrich, T., Lemaire, H.G., Schenkman, S., Tanaka, A.S., 2002. Infestin, a thrombin inhibitor presents in Triatoma infestans midgut, a Chagas’ disease vector: gene cloning, expression and characterization of the inhibitor. Insect Biochem. Mol. Biol. 32, 991–997.PubMedCrossRefGoogle Scholar
- Macedo-Ribeiro, S., Almeida, C., Calisto, B.M., Friedrich, T., Mentele, R., Sturzebecher, J., Fuentes-Prior, P., Pereira, P.J., 2008. Isolation, cloning and structural characterisation of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick. PLoS One 3, e1624PubMedCrossRefGoogle Scholar
- Mende, K., Petoukhova, O., Koulitchkova, V., Schaub, G.A., Lange, U., Kaufmann, R., Nowak, G., 1999. Dipetalogastin, a potent thrombin inhibitor from the blood-sucking insect. Dipetalogaster maximus cDNA cloning, expression and characterization. Eur. J. Biochem. 266, 583–590.PubMedCrossRefGoogle Scholar