A structural view on the functional importance of the sugar moiety and steroid hydroxyls of cardiotonic steroids in binding to Na,K-ATPase

Journal of Biological Chemistry

Volumn 288, Issue 9, 2013, Pages 6602-6616

  Cornelius, Flemming ^a   Kanai, Ryuta ^b   Toyoshima, Chikashi ^b  

^a AARHUS UNIVERSITY   (Denmark)

^b UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AGLYCONES; ANTI-CANCER AGENTS; CARDIOTONIC STEROIDS; CONGESTIVE HEART FAILURES; EXTRACELLULAR; HIGH PH; HYDROXYL GROUPS; PH VALUE; SUGAR MOIETY; SUGAR RESIDUES; THERAPEUTIC VALUES;

ENZYME ACTIVITY; LIPIDS;

SUGARS;

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); AGLYCONE; BUFALIN; CARDIOTONIC AGENT; CARDIOTONIC STEROID; DIGITOXIGENIN; DIGITOXIN; DIGOXIGENIN; DIGOXIGENIN DIDIGITOXIDE; DIGOXIGENIN MONODIGITOXIDE; DIGOXIGENIN TETRADIGITOXIDE; DIGOXIN; EVOMONOSIDE; GAMABUFOTALIN; GITOXIGENIN; GITOXIN; HYDROXYL GROUP; OUABAGENIN; OUABAIN; STEROID HYDROXYL; STROPHANTHIDIN; STROPHANTHIDOL; SUGAR; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME REACTIVATION; PH; PRIORITY JOURNAL;

ANIMALS; CARDIAC GLYCOSIDES; ENZYME INHIBITORS; ENZYME STABILITY; FISH PROTEINS; HYDROGEN-ION CONCENTRATION; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; SODIUM-POTASSIUM-EXCHANGING ATPASE; SQUALUS ACANTHIAS;

EID: 84874782025     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.442137     Document Type: Article

References (56)

1. Schatzmann, H. J. (1953) Hertzglycoside als hemmstoffe für den aktiven kalium- und natriumtransport durch die erythrocytenmembran. Helv. Physiol. Pharmacol. Acta 11, 346-354
2. Mijatovic, T., Dufrasne, F., and Kiss, R. (2012) Cardiotonic steroids-mediated targeting of the Na+/K+-ATPase to combat chemoresistant cancers. Curr. Med. Chem. 19, 627-646
3. Prassas, I., and Diamandis, E. P. (2008) Novel therapeutic applications of cardiac glycosides. Nat. Rev. Drug Discov. 7, 926-935
4. Wang, H.-Y., and O'Doherty, G. A. (2012) Modulators of Na/K-ATPase.A patent review. Expert Opin. Ther. Pat. 22, 587-605
5. Yoda, A. (1973) Structure-activity relationships of cardiotonic steroids for the inhibition of sodium- and potassium-dependent adenosine triphosphatase. I. Dissociation rate constants of various enzyme-cardiac glycoside complexes formed in the presence of magnesium and phosphate. Mol. Pharmacol. 9, 51-60
6. Dostanic-Larson, I., Van Huysse, J. W., Lorenz, J. N., and Lingrel, J. B (2005) The highly conserved cardiac glycoside binding site of Na,KATPase plays a role in blood pressure regulation. Proc. Natl. Acad. Sci. U.S.A. 102, 15845-15850
7. Yoda, A., and Yoda, S. (1982) Interaction between ouabain and the phosphorylated intermediate of Na,K-ATPase. Mol. Pharmacol. 22, 700-705
8. Cornelius, F., Mahmmoud, Y. A., and Toyoshima, C. (2011) Metal fluoride complexes of Na,K-ATPase. Characterization of fluoride-stabilized phosphoenzyme analogues and their interaction with cardiotonic steroids. J. Biol. Chem. 286, 29882-29892
9. Ogawa, H. Shinoda, T., Cornelius, F., and Toyoshima, C. (2009). Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain. Proc. Natl. Acad. Sci. U.S.A. 106, 13742-13747
10. Toyoshima, C., Norimatsu, Y., Iwasawa, S., Tsuda, T., and Ogawa, H. (2007) How processing of aspartylphosphate is coupled to lumenal gating of the ion pathway in the calcium pump. Proc. Natl. Acad. Sci. U.S.A. 104, 19831-19836
11. Olesen, C., Picard, M., Winther, A.-M., Gyrup, C., Morth, J. P., Oxvig, C., Møller, J. V., and Nissen, P. (2007) The structural basis of calcium transport by the calcium pump. Nature 450, 1036-1042
12. Akera, T., Brody, T. M. (1971) Membrane adenosine triphosphatase. The effect of potassium on the formation and dissociation of the ouabainenzyme complex. J. Pharmacol. Exp. Ther. 176, 545-557
13. Tobin, T., and Brody, T. M. (1972) Rates of dissociation of enzyme-ouabain complexes and K0.5 values in (Na+ + K+) adenosine triphosphatase from different species. Biochem. Pharmacol. 21, 1553-1560
14. Yatime, L., Laursen, M., Morth, J. P., Esmann, M., Nissen, P., and Fedosova, N. (2011) Structural insight into the high affinity binding of cardiotonic steroids to the Na+,K+-ATPase. J. Struct. Biol. 174, 296-306
15. Toyoshima, C., Kanai, R., and Cornelius, F. (2011) First crystal structures of Na+,K+-ATPase. New light on the oldest ion pump. Structure 19, 1732-1738
16. Cornelius, F., and Mahmmoud, Y. A. (2009) Interaction between cardiotonic steroids and Na,K-ATPase. Effects of pH and ouabain-induced changes in enzyme conformation. Biochemistry 48, 10056-10065
17. Skou, J. C., and Esmann, M. (1988) Preparation of membrane Na+,K+- ATPase from rectal glands of Squalus acanthias. Methods Enzymol. 156, 43-46
18. Mahmmoud, Y. A., Vorum, H., and Cornelius, F. (2000) Identification of a phospholemman-like protein from shark rectal glands. Evidence for indirect regulation of Na,K-ATPase by protein kinase C via a novel member of the FXYDY family. J. Biol. Chem. 275, 35969-35977
19. Peterson, G. L. (1983) Determination of total protein. Methods Enzymol. 91, 95-119
20. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265-275
21. Baginski, E. S., Foa, P. P., Zak, B. (1967) Determination of phosphate. Study of labile organic phosphate interference. Clin. Chim. Acta 14, 155-158
22. Fiske, C. H., and SubbaRow, Y. (1925) The colorimetric determination of phosphorus. J. Biol. Chem. 66, 375-400
23. Grell, E., Lewitzki, E., Schacht, A., and Stolz, M. (2004) Nucleotide/protein interaction. Energetic and structural features of Na,K-ATPase. J. Therm. Anal. Calorim. 77, 471-481
24. Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. S., Kuszewski, J., Nilges, M., Pannu, N. S., Read, R. J., Rice, L. M., Simonson, T., Warren, G. L. (1998) Crystallography and NMR system. A new software suite for macromolecular structure determination. Acta Crystallogr. D 54, 905-921
25. Kleywegt, G. J. (2007) Crystallographic refinement of ligand complexes. Acta Crystallogr. D 63, 94-100
26. Paula, S., Tabet, M. R., Ball, W. J., Jr. (2005) Interactions between cardiac glycosides and sodium/potassium-ATPase. Three-dimensional structureactivity relationship models for ligand binding to the E2-Pi form of the enzyme versus activity inhibition. Biochemistry 44, 498-510
27. Katz, A., Lifshitz, Y., Bab-Dinitz, E., Kapri-Pardes, E., Goldshleger, R., Tal, D. M., and Karlish, S. J. (2010) Selectivity of digitalis glycosides for isoforms of human Na,K-ATPase. J. Biol. Chem. 285, 19582-19592
28. Farr, C. D., Burd, C., Tabet, M. R., Wang, X., Welsh, W. J., and Ball, W. J., Jr. (2002) Three-dimensional quantitative structure-activity relationship study of the inhibition of Na+,K+-ATPase by cardiotonic steroids using comparative molecular field analysis. Biochemistry 41, 1137-1148
29. Brown, L., Erdmann, E., and Thomas, R. (1983) Digitalis structure-activity relationship analyses. Conclusions from indirect binding studies with cardiac (Na+ + K+)-ATPase. Biochem. Pharmacol. 32, 2767-2774
30. Grell, E., Schick, E., and Lewitzki, E. (2001) Membrane receptor calorimetry. Cardiac glycoside interaction with Na,K-ATPase. Thermochim. Acta 380, 245-254
31. Yoda, A., and Yoda, S. (1978) Influence of pH on the interaction of cardiotonic steroids with sodium- and potassium-dependent adenosine triphosphatase. Mol. Pharmacol. 14, 624-632
32. Yoda, S., Sharrif, A. M., and Yoda, A. (1975) Structure-activity relationships of cardiotonic steroids for the inhibition of sodium- and potassiumdependent adenosine triphosphatase. IV. Dissociation rate constants for complexes of the enzyme with cardiac oligodigitoxides. Mol. Pharmacol. 11, 647-652
33. Griffin, J. F., Rohrer, D. C., Ahmed, K., From, A. H., Hashimoto, T., Rathore, H., and Fullerton, D. S. (1986) The effect of 16β-substitution on the structure and activity of digitoxigenin. Is there an additional binding interaction with Na+,K+-ATPase? Mol. Pharmacol. 29, 270-274
34. Repke, K. R. (1985) New developments in cardiac glycoside structureactivity relationships. Trends Pharmacol. Sci. 6, 275-278
35. Yoda, A., and Yoda, S. (1977) Association and dissociation rate constants of the complexes between various cardiac aglycones and sodium- and potassium-dependent adenosine triphosphatase formed in the presence of magnesium and phosphate. Mol. Pharmacol. 13, 352-361
36. Feng, J., and Lingrel, J. B (1994) Analysis of amino acid residues in the H5-H6 transmembrane and extracellular domains of Na,K-ATPase α subunit identifies threonine 797 as a determinant of ouabain sensitivity. Biochemistry 33, 4218-4224
37. Qiu, L. Y., Koenderink, J. B., Swarts, H. G., Willems, P. H., De Pont, J. J. (2003) Phe783, Thr797, and Asp804 in transmembrane hairpin M5-M6 of Na+,K+-ATPase play a key role in ouabain binding. J. Biol. Chem. 278, 47240-47244
38. Qiu, L. Y., Swarts, H. G., Tonk, E. C., Willems, P. H., Koenderink, J. B., De Pont, J. J. (2006) Conversion of the low-affinity ouabain-binding site of non-gastric H,K-ATPase into a high-affinity binding site by substitution of only five amino acids. J. Biol. Chem. 281, 13533-13539
39. Radkov, R., Kharoubi-Hess, S., Schaer, D., Modyanov, N. N., Geering, K., Horisberger, J. D. (2007) Role of homologous ASP334 and GLU319 in human non-gastric H,K- and Na,K-ATPases in cardiac glycoside binding. Biochem. Biophys. Res. Commun. 356, 142-146
40. Price, E. M., Rice, D. A., Lingrel, J. B (1990) Structure-function studies of Na,K-ATPase. Site-directed mutagenesis of the border residues from the H1-H2 extracellular domain of the α subunit. J. Biol. Chem. 265, 6638-6641
41. Yoda, A., Yoda, S., and Sarrif, A. M. (1973) Structure-activity relationships of cardiotonic steroids for the inhibition of sodium- and potassium-dependent adenosine triphosphate. II. Association rate constants of various enzyme-cardiac glycoside complexes. Mol. Pharmacol. 9, 766-773
42. Lingrel, J. B., Argüello, J. M., Van Huysse, J., Kuntzweiler, T. A. (1997) Cation and cardiac glycoside binding sites of the Na,K-ATPase. Ann. N.Y. Acad. Sci. 834, 194-206
43. Lingrel, J. B, Orlowski, J., Rice, D. A., and Pathak, B. G. (1991) Regulation of the α-subunit genes of the Na,K-ATPase and determinants of cardiac glycoside sensitivity. Soc. Gen. Physiol. Ser. 46, 1-16
44. Rodacher, V, Toustrup-Jensen, M., and Vilsen, B. (2006) Mutations Phe785Leu and Thr618Met in Na+,K+-ATPase, associated with familial rapid-onset dystonia parkinsonism, interfere with Na+ interaction by distinct mechanisms. J. Biol. Chem. 281, 18539-18548
45. Qiu, L. Y., Krieger, E., Schaftenaar, G., Swarts, H. G., Willems, P. H., De Pont, J. J., Koenderink, J. B. (2005) Reconstruction of the complete ouabain- binding pocket of Na,K-ATPase in gastric H,K-ATPase by substitution of only seven amino acids. J. Biol. Chem. 280, 32349-32355
46. Kamano, Y., Kotake, A., Hashima, H., Inoue, M., Morita, H., Takeya, K., Itokawa, H., Nandachi, N., Segawa, T., Yukita, A., Saitou, K., Katsuyama, M., and Pettit, G. R. (1998) Structure-cytotoxic activity relationship for the toad poison bufadienolides. Bioorg. Med. Chem. 6, 1103-1115
47. Go, K., and Kartha, G. (1980) Structure of gitoxin. Acta Crystallogr. B 36, 3034-3040
48. De Pover, A., and Godfraind, T. (1982) Influence of 16β-formylation on Na,K-ATPase inhibition by cardiac glycosides. Naunyn-Schmiedebergs Arch. Pharmacol. 321, 135-139
49. Woodcock, B. G., and Rietbrock, N. (1985) The forgotten cardiac glycoside of Digitalis purpurea. Trends Pharmacol. Sci. 6, 273-275
50. Hashimoto, T., Rathore, H., Satoh, D., Hong, G., Griffin, J. F., From, A. H., Ahmed, K., and Fullerton, D. S. (1986) Cardiac glycosides. 6. Gitoxigenin C16 Acetates, Formates, Methoxycarbonates, and Digitoxosides. Synthesis and Na+,K+-ATPase inhibitory activity. J. Med. Chem. 29, 997-1003
51. Fullerton, D. S., Yoshioka, K., Rohrer, D. C., From, A. H., and Ahmed, K. (1979) Digitalis genin activity. Side-group carbonyl oxygen position is a major determinant. Science 205, 917-919
52. Ahmed, K., Rohrer, D. C., Fullerton, D. S., Deffo, T., Kitatsuji, E., and From, A. H. (1983) Interaction of (Na+,K+)-ATPase and digitalis genins. A general model for inhibitory activity. J. Biol. Chem. 258, 8092-8097
53. Fullerton, D. S., Kitatsuji, E., Deffo, T., Roher, D. C., Ahmed, K., and From, A. H. L. (1983) Use of prophet and MMS-X computer graphics in the study of the cardiac steroid receptor site of Na,K-ATPase. Curr. Top. Membr. Transp. 19, 257-264
54. Poulsen, H., Khandelia, H., Morth, J. P., Bublitz, M., Mouritsen, O. G., Egebjerg, J., and Nissen, P. (2010) Neurological disease mutations comprise a C-terminal ion pathway in the Na+/K+-ATPase. Nature 467, 99-102
55. Schneeberger, A., and Apell, H.-J. (2001) Ion selectivity of the cytoplasmic binding sites of the Na,K-ATPase. II. Competition of various cations. J. Membr. Biol. 179, 263-273
56. Thomas, R., Boutagy, J., and Gelbart, A. (1974) Cardenolide analogs. V. Cardiotonic activity of semisynthetic analogs of digitoxigenin. J. Pharmacol. Exp. Ther. 191, 219-231