Dynamic properties of the native free antithrombin from molecular dynamics simulations: Computational evidence for solvent- exposed Arg393 side chain

Journal of Biomolecular Structure and Dynamics

Volumn 33, Issue 9, 2015, Pages 2023-2036

  Tóth, László ^a   Fekete, Attila ^a   Balogh, Gábor ^a   Bereczky, Zsuzsanna ^a   Komáromi, István ^a,b  

^a UNIVERSITY OF DEBRECEN   (Hungary)

^b UNIVERSITY OF DEBRECEN   (Hungary)

Author keywords

allostery; antithrombin; fluctuation; generalized correlation; molecular dynamics simulation; principal component analysis; reactive center loop; serpin structure

Indexed keywords

ANTITHROMBIN; HEPARIN; PENTASACCHARIDE; ANTITHROMBIN III; SOLVENT; THROMBIN;

ALLOSTERISM; AMINO ACID SEQUENCE; ARTICLE; BINDING SITE; COMPLEX FORMATION; COMPUTER MODEL; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; HELIX D; HELIX P; MOLECULAR DYNAMICS; PRINCIPAL COMPONENT ANALYSIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN SECONDARY STRUCTURE; PROTEIN STRUCTURE; REACTIVE CENTER LOOP; RNA TRANSLATION; STRUCTURE ANALYSIS; ANALOGS AND DERIVATIVES; CHEMISTRY; HUMAN; X RAY CRYSTALLOGRAPHY;

ALLOSTERIC REGULATION; AMINO ACID SEQUENCE; ANTITHROMBIN III; ANTITHROMBINS; CRYSTALLOGRAPHY, X-RAY; HEPARIN; HUMANS; MOLECULAR DYNAMICS SIMULATION; PROTEIN CONFORMATION; SOLVENTS; THROMBIN;

EID: 84937635746     PISSN: 07391102     EISSN: 15380254     Source Type: Journal    
DOI: 10.1080/07391102.2014.986525     Document Type: Article

References (67)

1. Arocas, V., Bock, S. C., Raja, S. M., Olson, S. T., & Björk, I. (2011). Lysine 114 of antitrombin is of crucial importance for the affinity and kinetics of heparin pentasaccharide binding. Journal of Biological Chemistry, 276, 43809-43817. doi:10.1074/jbc.M105294200
2. Bakan, A., Meireles, L., & Bahar, I. (2009). ProDy: protein dynamics inferred from theory and experiments. Bioinformatics, 27, 1575-1577. doi:10.1093/bioinformatics/btr168
3. Barducci, A., Bonomi, M., & Parinello, M. (2011). Metadynamics. Wiley Interdisciplinary Reviews-Computational Molecular Science, 1, 826-843. doi:10.1002/Wcms.31
4. Bedsted, T., Swanson, R., Chuang, Y. J., Bock, P. E., Björk, I., & Olson, S. T. (2003). Heparin and calcium ions dramatically enhance antithrombin reactivity with factor IXa by generating new interaction exosites. Biochemistry, 42, 8143-8152.
5. Berendsen, H. J. C., Postma, J. P. M., DiNola, A., & Haak, J. R. (1984). Molecular dynamics with coupling to an external bath. The Journal of Chemical Physics, 81, 3684-3690. doi:10.1063/1.448118
6. Berendsen, H. J. C., & van Gunsteren, W. F. (1984). Molecular dynamics simulations: Techniques and approaches. In A. J. Barnes, W. J. Orville-Thomas, & J. J. Yarwood (Eds.), Molecular liquids - Dynamics and interactions (Vol. 135, pp. 475-500). Dordrecht: Reidel.
7. Björk, I., & Olson, S. T. (1997). Antithrombin. A bloody important serpin. Advances in Experimental Medicine and Biology, 425, 17-33.
8. Bray, B., Lane, D. A., Freyssinet, J. M., Pejler, G., & Lindahl, U. (1989). Anti-thrombin activities of heparin. Effect of saccharide chain length on thrombin inhibition by heparin cofactor II and by antithrombin. Biochemical Journal, 262, 225-232.
9. Bussi, G., Donadio, D., & Parrinello, M. (2007). Canonical sampling through velocity rescaling. The Journal of Chemical Physics, 126, 014101.
10. Chandrasekaran, V., Lee, C. J., Lin, P., Duke, R. E., & Pedersen, L. G. (2009). A computational modeling and molecular dynamics study of the Michaelis complex of human protein Z-dependent protease inhibitor (ZPI) and factor Xa (FXa). Journal of Molecular Modeling, 15, 897-911.
11. Cui, Q., & Karplus, M. (2008). Allostery and cooperativity revisited. Protein Science, 17, 1295-1307. doi:10.1110/ps.03259908
12. Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: An N•log(N) method for Ewald sums in large systems. The Journal of Chemical Physics, 98, 10089-10092.
13. dela Cruz, R. G., Jairajpuri, M. A., & Bock, S. C. (2006). Disruption of a Tight Cluster Surrounding Tyrosine 131 in the Native Conformation of Antithrombin III Activates It for Factor Xa Inhibition. Journal of Biological Chemistry, 281, 31668-31676.
14. Dementiev, A., Petitou, M., Herbert, J. M., & Gettins, P. G. (2004). The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity. Nature Structural & Molecular Biology, 11, 863-867.
15. Desai, U., Swanson, R., Bock, S. C., Björk, I., & Olson, S. T. (2000). Role of arginine 129 in heparin binding and activation of antithrombin. Journal of Biological Chemistry, 275, 18976-18984.
16. Duan, Y., Wu, C., Chowdhury, S., Lee, M. C., Xiong, G., Zhang, W., ... Kollman, P. (2003). A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. Journal of Computational Chemistry, 24, 1999-2012.
17. Dunstone, M., & Whisstock, J. (2011). Crystallography of serpins and serpin complexes. Methods in Enzymology, 501, 63-87. doi:10.1016/B978-0-12-385950-1.00005-5
18. Fiser, A., & Šali, A. (2003). Modeller: Generation and refinement of homology-based protein structure models. Methods in Enzymology, 374, 461-491.
19. Gettins, P. G. (2002). Serpin structure, mechanism, and function. Chemical Reviews, 102, 4751-4804. doi:10.1021/cr010170+
20. Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14, 33-38.
21. Huntington, J. A. (2005). Heparin activation of serpins. In H. G. Garg, R. J. Linhardt, & C. A. Hales (Eds.), Chemistry and biology of heparin and heparan sulfate (pp. 367-398). Oxford: Elsevier.
22. Huntington, J. A. (2011). Serpin structure, function and dysfunction. Journal of Thrombosis and Haemostasis, 9, 26-34. doi:10.1111/j.1538-7836.2011.04360.x
23. Ichiye, T., & Karplus, M. (1991). Collective motions in proteins: A covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations. Proteins: Structure, Function, and Genetics, 11, 205-217. doi:10.1002/prot.340110305
24. Izaguirre, G., & Olson, S. T. (2006). Residues Tyr253 and Glu255 in strand 3 of beta-sheet C of antithrombin are key determinants of an exosite made accessible by heparin activation to promote rapid inhibition of factors Xa and IXa. Journal of Biological Chemistry, 281, 13424-13432. doi:10.1074/jbc.M600415200
25. Jacobson, M. P., Pincus, D. L., Rapp, C. S., Day, T. J., Honig, B., Shaw, D. E., & Friesner, R. A. (2004). A hierarchical approach to all-atom protein loop prediction. Proteins: Structure, Function, and Bioinformatics, 55, 351-367.
26. Jairajpuri, M. A., Lu, A., Desai, U., Olson, S. T., Björk, I., & Bock, S. C. (2003). Antithrombin III phenylalanines 122 and 121 contribute to its high affinity for heparin and its conformational activation. Journal of Biological Chemistry, 278, 15941-15950.
27. Johnson, D. J. D., & Huntington, J. A. (2003). Crystal structure of antithrombin in a heparin-bound intermediate state. Biochemistry, 42, 8712-8719.
28. Johnson, D. J. D., Langdown, J., Li, W., Luis, S. A., Baglin, T. P., & Huntington, J. A. (2006). Crystal structure of monomeric native antithrombin reveals a novel reactive center loop conformation. Journal of Biological Chemistry, 281, 35478-35486.
29. Johnson, D. J., Langdown, J., & Huntington, J. A. (2010). Molecular basis of factor IXa recognition by heparin-activated antithrombin revealed by a 1.7-A structure of the ternary complex. Proceedings of the National Academy of Sciences, 107, 645-650.
30. Johnson, D. J., Li, W., Adams, T. E., & Huntington, J. A. (2006). Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation. The EMBO Journal, 25, 2029-2037.
31. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., & Klein, M. L. (1983). Comparison of simple potential functions for simulating liquid water. The Journal of Chemical Physics, 79, 926-935. doi:10.1063/1.445869
32. Kabsch, W., & Sander, C. (1983). Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 22, 2577-2637.
33. Kass, I., Knaupp, A. S., Bottomley, S. P., & Buckle, A. M. (2012). Conformational properties of the disease-causing Z variant of alpha1-antitrypsin revealed by theory and experiment. Biophysical Journal, 102, 2856-2865.
34. Kass, I., Reboul, C. F., & Buckle, A. M. (2011). Computational methods for studying serpin conformational change and structural plasticity. Methods in Enzymology, 501, 295-323.
35. Langdown, J., Belzar, K. J., Savory, W. J., Baglin, T. P., & Huntington, J. A. (2009). The critical role of hinge-region expulsion in the induced-fit heparin binding mechanism of antithrombin. Journal of Molecular Biology, 386, 1278-1289.
36. Langdown, J., Carter, W. J., Baglin, T. P., & Huntington, J. A. (2006). Allosteric activation of antithrombin is independent of charge neutralization or reversal in the heparin binding site. FEBS Letters, 580, 4709-4712.
37. Lange, O. F., & Grubmuller, H. (2006). Generalized correlation for biomolecular dynamics. Proteins, 62, 1053-1061. doi:10.1002/prot.20784
38. Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. Journal of Applied Crystallography, 26, 283-291.
39. Lee, M. C., & Duan, Y. (2004). Distinguish protein decoys by using a scoring function based on a new AMBER force field, short molecular dynamics simulations, and the generalized born solvent model. Proteins: Structure, Function, and Bioinformatics, 55, 620-634. doi:10.1002/prot.10470
40. Li, W., Johnson, D. J., Esmon, C. T., & Huntington, J. A. (2004). Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nature Structural & Molecular Biology, 11, 857-862.
41. McCoy, A. J., Pei, X. Y., Skinner, R., Abrahams, J. P., & Carrell, R. W. (2003). Structure of beta-antithrombin and the effect of glycosylation on antithrombin's heparin affinity and activity. Journal of Molecular Biology, 326, 823-833.
42. Monien, B. H., Krishnasamy, C., Olson, S. T., & Desai, U. R. (2005). Importance of tryptophan 49 of antithrombin in heparin binding and conformational activation. Biochemistry, 44, 11660-11668.
43. Muszbek, L., Bereczky, Z., Kovacs, B., & Komaromi, I. (2010). Antithrombin deficiency and its laboratory diagnosis. Clinical Chemistry and Laboratory Medicine, 48, S67-S78.
44. Olson, S. T., Bjork, I., et al. (1992). Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. Journal of Biological Chemistry, 267, 12528-12538.
45. Olson, S. T., Bjork, I., Sheffer, R., Craig, P. A., Shore, J. D., & Choay, J. (2002). Identification of critical molecular interactions mediating heparin activation of antithrombin: Implications for the design of improved heparin anticoagulants. Trends in Cardiovascular Medicine, 12, 198-205.
46. Olson, S. T., Richard, B., Izaguirre, G., Schedin-Weiss, S., & Gettins, P. G. (2010). Molecular mechanisms of antithrombin-heparin regulation of blood clotting proteinases. A paradigm for understanding proteinase regulation by serpin family protein proteinase inhibitors. Biochimie, 92, 1587-1596.
47. Owen, M. C., Beresford, C. H., & Carrell, R. W. (1988). Antithrombin Glasgow, 393 arg to his: A P1 reactive site variant with increased heparin affinity but no thrombin inhibitory activity. FEBS Letters, 231, 317-320.
48. Pronk, S., Pall, S., Schulz, R., Larsson, P., Bjelkmar, P., Apostolov, R., & Lindahl, E. (2013). GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics, 29, 845-854.
49. Quinsey, N. S., Greedy, A. L., Bottomley, S. P., Whisstock, J. C., & Pike, R. N. (2004). Antithrombin: In control of coagulation. International Journal of Biochemistry & Cell Biology, 36, 386-389.
50. Rau, J. C., Beaulieu, L. M., Huntington, J. A., & Church, F. C. (2007). Serpins in thrombosis, hemostasis and fibrinolysis. Journal of Thrombosis and Haemostasis, 5, 102-115.
51. Rezaie, A. R. (1998). Calcium enhances heparin catalysis of the antithrombin-factor Xa reaction by a template mechanism. Evidence that calcium alleviates Gla domain antagonism of heparin binding to factor Xa. Journal of Biological Chemistry, 273, 16824-16827. doi: 10.1074/jbc.273.27.16824
52. Rezaie, A. R., & Olson, S. T. (2000). Calcium enhances heparin catalysis of the antithrombin-factor Xa reaction by promoting the assembly of an intermediate heparin-antithrombin-factor Xa bridging complex. Demonstration by rapid kinetics studies. Biochemistry, 39, 12083-12090. doi: 10.1021/bi0011126
53. Schedin-Weiss, S., Desai, U. R., Bock, S. C., Gettins, P. G., Olson, S. T., & Björk, I. (2002). Importance of lysine 125 for heparin binding and activation of antithrombin. Biochemistry, 41, 4779-4788.
54. Schedin-Weiss, S., Richard, B., & Olson, S. T. (2010). Kinetic evidence that allosteric activation of antithrombin by heparin is mediated by two sequential conformational changes. Archives of Biochemistry and Biophysics, 504, 169-176.
55. Schlick, T. (2010). Molecular modeling and simulation: An interdisciplinary guide. New York, NY: Springer.
56. Schreuder, H. A., de Boer, B., Dijkema, R., Mulders, J., Theunissen, H. J., Grootenhuis, P. D., & Hol, W. G. (1994). The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions. Nature Structural Biology, 1, 48-54.
57. SchrödingerLLC. (2013). Schrödinger Release 2013-2: Prime. New York, NY: Schrödinger, LLC.
58. Seegers, W. H., Johnson, J. F., & Fell, C. (1954). An antithrombin reaction to prothrombin activation. American Journal of Physiology, 176, 97-103.
59. Silverman, G. A., Bird, P. I., Carrell, R. W., Church, F. C., Coughlin, P. B., Gettins, P. G., ... Whisstock, J. C. (2001). The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. Journal of Biological Chemistry, 276, 33293-33296.
60. Tribello, G. A., Bonomi, M., Branduardi, D., Camilloni, C., & Bussi, G. (2014). PLUMED 2: New feathers for an old bird. Computer Physics Communications, 185, 604-613.
61. van der Spoel, D., Lindahl, E., Hess, B., van Buuren, A. R., Apol, E., Meulenhoff, P. J., ... Berendsen, H. J. C. (2010). Gromacs User Manual version 4.5.4. Retrieved from www.gromacs.org.
62. Van Wart, A. T., Durrant, J., Votapka, L., & Amaro, R. E. (2014). Weighted implementation of suboptimal paths (WISP): An optimized algorithm and tool for dynamical network analysis. Journal of Chemical Theory and Computation, 10, 511-517.
63. Van Wynsberghe, A. W., & Cui, Q. (2006). Interpreting correlated motions using normal mode analysis. Structure, 14, 1647-1653. doi: 10.1016/j.str.2006.09.003
64. Verli, H., & Guimarães, J. A. (2005). Insights into the induced fit mechanism in antithrombin-heparin interaction using molecular dynamics simulations. Journal of Molecular Graphics and Modelling, 24, 203-212. doi: 10.1016/j.jmgm.2005.07.002
65. Villoutreix, B. O., & Sperandio, O. (2010). In silico studies of blood coagulation proteins: From mosaic proteases to nonenzymatic cofactor inhibitors. Current Opinion in Structural Biology, 20, 168-179. doi: 10.1016/j.sbi.2009.12.016
66. Whisstock, J. C., & Bottomley, S. P. (2006). Molecular gymnastics: Serpin structure, folding and misfolding. Current Opinion in Structural Biology, 16, 761-768. doi: 10.1016/j.sbi.2006.10.005
67. Whisstock, J. C., Pike, R. N., Jin, L., Skinner, R., Pei, X. Y., Carrell, R. W., & Lesk, A. M. (2000). Conformational changes in serpins: II. The mechanism of activation of antithrombin by heparindagger. Journal of Molecular Biology, 301, 1287-1305.