Abstract
The interactions between thrombin and synthetic or natural (polypeptide) inhibitors has been well characterized at the atomic level by x-ray crystallography as evidenced by the spectacular progress outlined elsewhere in this book. In some cases, however, elements of structural disorder in the x-ray picture are clouded by uncertainties as to the origins of this disorder: multiple conformers of the protein crystal packing effects or real conformational changes resulting from the enzyme:inhibitor interaction.
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References
H.A. Scheraga, K. Gibson, and F. Ni, NMR studies of thrombin-fibrinopeptide and thrombin-hirudin complexes, in: “Thrombin: Structure and Function,” Berliner, L. J. (ed.), Plenum Publishing, New York, NY. pp. 63 (1992).
S.R. Stone, J. and Hofsteenge, Kinetics of the inhibition of thrombin by hirudin, Biochemistry 25: 4622 (1986).
L.J. Berliner, Using the spin label method in enzymology, in: “Spectroscopy in Biochemistry, Vol. 2,” J. E. Bell, ed. CRC Press, Boca Raton, Florida pp. 1 (1980).
L.J. Berliner, ESR and fluorescence studies of thrombin active site conformation, in: Thrombin: Structure and Function, L.J. Berliner, ed. Plenum Publishing, New York, NY pp. 87 (1992).
L.J. Berliner, and Y.Y.L. Shen, Active site fluorescent labelled dansyl and anthraniloyl human thrombins, Thromb. Res. 12: 15 (1977).
G. Musci, L.J. Berliner, and C.T. Esmon C.T, Evidence for multiple conformational changes in the active center of thrombin induced by complex formation thrombomodulin: an analysis employing nitroxide spin labels, Biochemistry 27: 769 (1988).
T.J. Rydel, K.G. Ravichandran, A. Tulinsky, W. Bode, R. Huber, C. Roitsch, and J.H. Fenton Jr., The structure of a complex of recombinant hirudin and human a-thrombin, Science 249: 277 (1990).
T.J. Rydel, and A Tulinsky, Refined structure of the hirudin-thrombin complex, J. Mol. Biol. 221: 583 (1991).
E. Skrzypczak-Jankun, V.E. Carperos, K.G. Ravichandran, and A. Tulinsky, Structure of the hirugen and hirulog 1 complexes of a-thrombin, J. Mol. Biol. 221: 1379 (1991).
W. Bode, R. Huber, T.J. Rydel, and A. Tulinsky, X-ray structure of human thrombin: structure of hirudin:thrombin complex, in: “Thrombin: Structure and Function,” Berliner, L. J. (ed.), Plenum Publishing, New York, NY. pp. 3 (1992).
W. Bode, I. Mayr, U. Baumann, R. Huber, S.R. Stone, and J. Hofsteenge, The refined 1.9 A crystal structure of human a-thrombin: Interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment, EMBO. J. 8: 3467 (1989).
S.A. Sonder, and J.W. Fenton, Jr. Differential inactivation of human and bovine a-thrombins by exosite affinity-labelling reagents, Thromb. Res. 32: 623 (1983).
R.L. Lundblad, M.E. Nesheim, D.L. Straight, S. Sailor, J. Bowie, J.W. Jenzano, J.D. Robert, and K.G. Mann, Bovine a-and ß-thrombin is not a consequence of reduced affinity for fibrinogen, J. Biol. Chem. 259: 6991 (1984).
R. Lottenberg, J.A. Hall, J.W. Fenton, Jr. and C.M. Jackson, The action of thrombin on peptide p-nitroanilide substrates: hydrolysis of tos-gly-pro-arg-pNA and D-phe-pip-arg-pNA by human a-and y-and bovine a-and ß-thrombins, Thromb. Res. 28: 313 (1982).
Y. Sugawara, J.J. Birktoft, and L.J. Berliner, Human a-and y-thrombin inhibition by trypsin inhibitors supports predictions from molecular graphics experiments, Seminars in Thrombosis and Hemostasis 12: 209 (1985).
L.J. Berliner, and Y.Y. Shen, Physical evidence for an apolar binding site near the catalytic center of human a-thrombin, Biochemistry 16: 4622 (1977b).
S. Kono, J.W. Fenton, Jr. and G.B. Villanueva, Analysis of the secondary structure of hirudin and the conformational change upon interaction with thrombin, Arch. Biochem. Biophys. 267: 158 (1988).
L.J. Berliner, R.S. Bauer, T-L. Chang, J.W. Fenton II, and Y.Y.L. Shen, Active site topography of human coagulant (a) and noncoagulant (y) thrombins, Biochemistry 20: 1831 (1981).
M.S. Brower, D.A. Walz, K.E. Garry, and J.W. Fenton, J.W. II, Human neutrophil elastase alters human a-thrombin function: Limited proteolysis near the y-cleavage site results in decreased fibrinogen clotting and platelet-stimulatory activity, Blood 69: 813 (1987).
D.V. Brezniak, M.J. Brower, J.I. Witting, D.A. Walz, and J.W. Fenton II, Human a-to t-thrombin cleavage occurs with neutrophil cathepsin G or chymotrypsin while retaining fibrinogen clotting activity, Biochemistry 29: 3536 (1989).
V.L. Nienaber, and L.J. Berliner, Conformational differences between human bovine thrombins as detected by electron spin resonance and fluorescence spectroscopy, Thromb. Haemostas. 65: 40 (1991).
J.K. Rowand, and L.J. Berliner, Structural differences in active site-labelled thrombin complexes with hirudin isoinhibitors, J. Protein Chem. 11: 483 (1992).
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Berliner, L.J., Woodford, J.K. (1993). Biophysical Studies of Interactions of Hirudin Analogs with Bovine and Human Thrombin by ESR and Fluorescence Labelling Studies. In: Claeson, G., Scully, M.F., Kakkar, V.V., Deadman, J. (eds) The Design of Synthetic Inhibitors of Thrombin. Advances in Experimental Medicine and Biology, vol 340. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-2418-6_5
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