European Biophysics Journal

, 39:3

Mechanism of allosteric effects of ATP on the kinetics of P-type ATPases



The roles of allosteric effects of ATP and protein oligomerisation in the mechanisms of P-type ATPases belong to the most controversial and least well understood topics in the field. Recent crystal structural and kinetic data, however, now allow certain hypotheses to be definitely excluded and consistent hypotheses to be developed. The aim of this review is to critically discuss recent results and, in the light of them, to present a set of conclusions which could form the basis of future research. The major conclusions are: (1) at saturating ATP concentrations P-type ATPases function as monomeric enzymes, (2) the catalytic units of P-type ATPases only possess a single ATP binding site, (3) at non-saturating ATP concentrations P-type ATPases exist as diprotomeric (or higher oligomeric) complexes, (4) protein–protein interactions within a diprotomeric complex enhances the enzymes’ ATP binding affinity, (5) ATP binding to both protomers within a diprotomeric complex causes it to dissociate into two separate monomers. The physiological role of protein–protein interactions within a diprotomer may be to enhance ATP binding affinity so as to scavenge ATP and maximize the ion pumping rate under hypoxic or anoxic conditions. For the first time a structural basis for the well-known ATP allosteric acceleration of the E2 → E1 transition is presented. This is considered to be due to a minimization of steric hindrance between neighbouring protomers because of the ability of ATP to induce a compact conformation of the enzymes’ cytoplasmic domains.


  1. Abe K, Kaya S, Imagawa T, Taniguchi K (2002) Gastric H/K-ATPase liberates two moles of Pi from one mole of phosphoenzyme formed from a high-affinity ATP binding site and one mole of enzyme-bound ATP at the low-affinity site during cross-talk between catalytic subunits. Biochemistry 41:2438–2445. doi:10.1021/bi015622r PubMedCrossRefGoogle Scholar
  2. Albers RW (1967) Biochemical aspects of active transport. Annu Rev Biochem 36:727–756. doi:10.1146/ PubMedCrossRefGoogle Scholar
  3. Andersen JP (1989) Monomer-oligomer equilibrium of sarcoplasmic reticulum Ca-ATPase and the role of subunit interaction in the Ca2+ pump mechanism. Biochim Biophys Acta 988:47–72PubMedGoogle Scholar
  4. Apell HJ, Diller A (2002) Do H+ ions obscure electrogenic Na+ and K+ binding in the E1 state of the Na+,K+-ATPase? FEBS Lett 532:198–202. doi:10.1016/S0014-5793(02)03675-X PubMedCrossRefGoogle Scholar
  5. Apell HJ, Roudna M, Corrie JET, Trentham DR (1996) Kinetics of phosphorylation of Na,K-ATPase by inorganic phosphate detected by a fluorescence method. Biochemistry 35:10922–10930. doi:10.1021/bi960238t PubMedCrossRefGoogle Scholar
  6. Askari A (1987) (Na+ + K+)-ATPase: on the number of the ATP sites of the functional unit. J Bioenerg Biomembr 19:359–374. doi:10.1007/BF00768539 PubMedCrossRefGoogle Scholar
  7. Askari A, Huang W (1982) Na+,K+-ATPase: evidence for the binding of ATP to the phosphoenzyme. Biochem Biophys Res Commun 104:1447–1453. doi:10.1016/0006-291X(82)91412-7 PubMedCrossRefGoogle Scholar
  8. Berberián G, Helguera G, Beaugé L (1993) ATP activation of plasma membrane yeast H+-ATPase shows complex kinetics independently of the degree of purification. Biochim Biophys Acta 1153:283–288. doi:10.1016/0005-2736(93)90417-X PubMedCrossRefGoogle Scholar
  9. Bishop JE, Al-Shawi MK, Inesi G (1987) Relationship of the regulatory nucleotide site to the catalytic site of the sarcoplasmic reticulum Ca-ATPase. J Biol Chem 262:4658–4663PubMedGoogle Scholar
  10. Blanco G, Koster JC, Mercer RW (1994) The α subunit of the Na+,K+-ATPase specifically and stably associates into oligomers. Proc Natl Acad Sci USA 91:8542–8546. doi:10.1073/pnas.91.18.8542 PubMedCrossRefGoogle Scholar
  11. Blostein R (1975) Na+ATPase of the mammalian erythrocyte membrane. Reversibility of phosphorylation at 0°. J Biol Chem 250:6118–6124PubMedGoogle Scholar
  12. Borlinghaus R, Apell HJ (1988) Current transients generated by the Na+/K+-ATPase after an ATP concentration jump: dependence on sodium and ATP concentration. Biochim Biophys Acta 939:197–206. doi:10.1016/0005-2736(88)90063-6 PubMedCrossRefGoogle Scholar
  13. Bühler R, Stürmer W, Apell HJ, Läuger P (1991) Charge translocation by the Na,K-pump: I. Kinetics of local field changes studied by time-resolved fluorescence measurements. J Membr Biol 121:141–161. doi:10.1007/BF01870529 PubMedCrossRefGoogle Scholar
  14. Buxbaum E, Schoner W (1990) Blocking of Na+/K+ transport by the MgPO4 complex analogue Co(NH3)4PO4 leaves the Na+/Na+-exchange reaction of the sodium pump unaltered and shifts its high affinity ATP-binding site to a Na+-like form. Eur J Biochem 193:355–360. doi:10.1111/j.1432-1033.1990.tb19346.x PubMedCrossRefGoogle Scholar
  15. Buxbaum E, Schoner W (1991) Phosphate binding and ATP-binding sites coexist in Na+/K+-transporting ATPase, as demonstrated by the inactivating MgPO4 complex analogue Co(NH3)4PO4. Eur J Biochem 195:407–419. doi:10.1111/j.1432-1033.1991.tb15720.x PubMedCrossRefGoogle Scholar
  16. Cable MB, Briggs FN (1988) Allosteric regulation of cardiac sarcoplasmic reticulum Ca-ATPase: a comparative study. Mol Cell Biochem 82:29–36. doi:10.1007/BF00242512 PubMedCrossRefGoogle Scholar
  17. Cable MB, Feher JJ, Briggs FN (1985) Mechanism of allosteric regulation of the Ca, Mg-ATPase of sarcoplasmic reticulum: studies with 5′-adenylyl methylenediphosphate. Biochemistry 24:5612–5619. doi:10.1021/bi00341a049 PubMedCrossRefGoogle Scholar
  18. Champeil P, Guillain F (1986) Rapid filtration of the phosphorylation-dependent dissociation of calcium from transport sites of purified sarcoplasmic reticulum ATPase and ATP modulation of the catalytic cycle. Biochemistry 25:7623–7633. doi:10.1021/bi00371a053 PubMedCrossRefGoogle Scholar
  19. Champeil P, Riollet S, Orlowski S, Guillain F, Seebregts CJ, McIntosh DB (1988) ATP regulation of sarcoplasmic reticulum Ca2+-ATPase. Metal-free ATP and 8-bromo-ATP bind with high affinity to the catalytic site of phosphorylated ATPase and accelerate dephosphorylation. J Biol Chem 263:12288–12294PubMedGoogle Scholar
  20. Clarke RJ, Kane DJ (2007) Two gears of ion pumping by the Na+,K+-ATPase. Biophys J 93:4187–4196. doi:10.1529/biophysj.107.111591 PubMedCrossRefGoogle Scholar
  21. Clarke RJ, Kane DJ, Apell H-J, Roudna M, Bamberg E (1998) Kinetics of Na+-dependent conformational changes of rabbit kidney Na+,K+-ATPase. Biophys J 75:1340–1353PubMedCrossRefGoogle Scholar
  22. Clarke RJ, Apell H-J, Kong BY (2007) Allosteric effect of ATP on Na+,K+-ATPase conformational kinetics. Biochemistry 46:7034–7044. doi:10.1021/bi700619s PubMedCrossRefGoogle Scholar
  23. Cornelius F (1995) Phosphorylation/dephosphorylation of reconstituted shark Na+,K+-ATPase: one phosphorylation site per αβ protomer. Biochim Biophys Acta 1235:197–204. doi:10.1016/0005-2736(95)80005-Z PubMedCrossRefGoogle Scholar
  24. Cornelius F (1999) Rate determination in phosphorylation of shark rectal Na,K-ATPase by ATP: temperature sensitivity and effects of ADP. Biophys J 77:934–942PubMedCrossRefGoogle Scholar
  25. Cornelius F, Fedosova NU, Klodos I (1998) E2P phosphoforms of Na,K-ATPase. II. Interaction of substrate and cation-binding sites in Pi phosphorylation of Na,K-ATPase. Biochemistry 37:16686–16696. doi:10.1021/bi981571v PubMedCrossRefGoogle Scholar
  26. Domaszewicz W, Apell HJ (1999) Binding of the third Na+ ion to the cytoplasmic side of the Na,K-ATPase is electrogenic. FEBS Lett 458:241–246. doi:10.1016/S0014-5793(99)01162-X PubMedCrossRefGoogle Scholar
  27. Donnet C, Arystarkhova E, Sweadner KJ (2001) Thermal denaturation of the Na,K-ATPase provides evidence for α-α oligomeric interaction and γ subunit association with the C-terminal domain. J Biol Chem 276:7357–7365. doi:10.1074/jbc.M009131200 PubMedCrossRefGoogle Scholar
  28. Esmann M (1984) The distribution of C12E8-solubilized oligomers of the (Na+ + K+)-ATPase. Biochim Biophys Acta 787:81–89PubMedGoogle Scholar
  29. Esmann M, Fedosova NU, Marsh D (2008) Osmotic stress and viscous retardation of the Na,K-ATPase ion pump. Biophys J 94:2767–2776. doi:10.1529/biophysj.106.101774 PubMedCrossRefGoogle Scholar
  30. Fedosova NU, Champeil P, Esmann M (2003) Rapid filtration analysis of nucleotide binding to Na,K-ATPase. Biochemistry 42:3536–3543. doi:10.1021/bi0268302 PubMedCrossRefGoogle Scholar
  31. Fendler K, Jaruschewski S, Hobbs A, Albers W, Froehlich JP (1993) Pre-steady state charge translocation in NaK-ATPase from eel electric organ. J Gen Physiol 102:631–666. doi:10.1085/jgp.102.4.631 PubMedCrossRefGoogle Scholar
  32. Forbush BIII (1987) Rapid release of 42K and 86Rb from an occluded state of the Na,K-pump in the presence of ATP or ADP. J Biol Chem 262:11104–11115PubMedGoogle Scholar
  33. Forbush BIII, Klodos I (1991) Rate-limiting steps in Na translocation by the Na/K pump. In: Kaplan JH, DeWeer P (eds) The sodium pump: structure, mechanism and regulation. Rockefeller University Press, New York, pp 211–225Google Scholar
  34. Frank J, Zouni A, van Hoek A, Visser AJWG, Clarke RJ (1996) Interaction of the fluorescent probe RH421 with ribulose-1, 5-bisphosphate carboxylase/oxygenase and with Na+,K+-ATPase membrane fragments. Biochim Biophys Acta 1280:51–64. doi:10.1016/0005-2736(95)00277-4 PubMedCrossRefGoogle Scholar
  35. Friedrich T, Bamberg E, Nagel G (1996) Na+,K+-ATPase pump currents in giant excised patches activated by an ATP concentration jump. Biophys J 71:2486–2500PubMedCrossRefGoogle Scholar
  36. Froehlich JP, Hobbs AS, Albers RW (1983) Evidence for parallel pathways of phosphoenzyme formation in the mechanism of ATP hydrolysis by electrophorus Na,K-ATPase. Curr Top Membr Transp 19:513–535Google Scholar
  37. Froehlich JP, Taniguchi K, Fendler K, Mahaney JE, Thomas DD, Albers RW (1997) Complex kinetic behaviour in the Na,K- and Ca-ATPases. Evidence for subunit-subunit interactions and energy conversion during catalysis. Ann N Y Acad Sci 834:280–296. doi:10.1111/j.1749-6632.1997.tb52259.x PubMedCrossRefGoogle Scholar
  38. González-Lebrero RM, Kaufman SB, Montes MR, Nørby JG, Garrahan PJ, Rossi RC (2002) The occlusion of Rb+ in the Na+/K+-ATPase. J Biol Chem 277:5910–5921. doi:10.1074/jbc.M105886200 PubMedCrossRefGoogle Scholar
  39. Grell E, Lewitzki E, Schacht A, Stolz M (2004) Nucleotide/protein interaction. Energetic and structural features of Na,K-ATPase. J Therm Anal Calorim 77:471–481. doi:10.1023/B:JTAN.0000038987.75618.33 CrossRefGoogle Scholar
  40. Gribble FM, Loussouarn G, Tucker SJ, Zhao C, Nichols CG, Ashcroft FM (2000) A novel method for measurement of submembrane ATP concentration. J Biol Chem 39:30046–30049. doi:10.1074/jbc.M001010200 CrossRefGoogle Scholar
  41. Hamer E, Schoner W (1993) Modification of the E1ATP binding site of Na+/K+-ATPase by the chromium complex of adenosine 5′-[β, γ-methylene]triphosphate blocks the overall reaction but not the partial activities of the E2 conformation. Eur J Biochem 213:743–748. doi:10.1111/j.1432-1033.1993.tb17815.x PubMedCrossRefGoogle Scholar
  42. Heegaard CW, le Maire M, Gulik-Krzywicki T, Møller JV (1990) Monomeric state and Ca2+ transport by sarcoplasmic reticulum Ca2+-ATPase, reconstituted with an excess of phospholipid. J Biol Chem 265:12020–12028PubMedGoogle Scholar
  43. Hegyvary C, Post RL (1971) Binding of adenosine triphosphate to sodium and potassium ion-stimulated adenosine triphosphatase. J Biol Chem 246:5234–5240PubMedGoogle Scholar
  44. Humphrey PA, Lüpfert C, Apell H-J, Cornelius F, Clarke RJ (2002) Mechanism of the rate-determining step of the Na+,K+-ATPase. Biochemistry 41:9496–9507. doi:10.1021/bi025836o PubMedCrossRefGoogle Scholar
  45. Inesi G, Toyoshima C (2004) Catalytic and transport mechanism of the sarco-(endo)plasmic reticulum Ca2+-ATPase (SERCA). In: Futai F, Wada Y, Kaplan JH (eds) Handbook of ATPases. Biochemistry, cell biology, pathophysiology. Wiley-VCH, Weinheim, pp 63–87Google Scholar
  46. Jensen A-ML, Sørensen TL-M, Olesen C, Møller JV, Nissen P (2006) Modulatory and catalytic modes of ATP binding by the calcium pump. EMBO J 25:2305–2314. doi:10.1038/sj.emboj.7601135 PubMedCrossRefGoogle Scholar
  47. Jørgensen PL, Andersen JP (1988) Structural basis for E1–E2 conformational transitions in Na,K-pump and Ca-pump proteins. J Membr Biol 103:95–120. doi:10.1007/BF01870942 PubMedCrossRefGoogle Scholar
  48. Kane DJ, Fendler K, Grell E, Bamberg E, Taniguchi K, Froehlich JP, Clarke RJ (1997) Stopped-flow kinetic investigations of conformational changes of pig kidney Na+,K+-ATPase. Biochemistry 36:13406–13420. doi:10.1021/bi970598w PubMedCrossRefGoogle Scholar
  49. Kane DJ, Grell E, Bamberg E, Clarke RJ (1998) Dephosphorylation kinetics of pig kidney Na+,K+-ATPase. Biochemistry 37:4581–4591. doi:10.1021/bi972813e PubMedCrossRefGoogle Scholar
  50. Karlish SJD, Yates DW (1978) Tryptophan fluorescence of (Na+ + K+)-ATPase as a tool for study of the enzyme mechanism. Biochim Biophys Acta 527:115–130PubMedGoogle Scholar
  51. Karlish SJD, Yates DW, Glynn IM (1976) Transient kinetics of (Na+ + K+)-ATPase studied with a fluorescent substrate. Nature 264:251–253. doi:10.1038/263251a0 CrossRefGoogle Scholar
  52. Karlish SJD, Yates DW, Glynn IM (1978) Conformational transitions between Na+-bound and K+-bound forms of (Na+ + K+)-ATPase, studied with formycin nucleotides. Biochim Biophys Acta 525:252–264PubMedGoogle Scholar
  53. Klein MG, Kovacs L, Simon BJ, Schneider MF (1991) Decline of myoplasmic Ca2+, recovery of calcium release and sarcoplasmic Ca2+ pump properties in frog skeletal muscle. J Physiol 414:639–671Google Scholar
  54. Klodos I (1994) Partial reactions in Na+/K+- and H+/K+-ATPase studied with voltage-sensitive fluorescent dyes. In: Bamberg E, Schoner W (eds) The sodium pump. Steinkopff Verlag, Darmstadt, pp 517–528Google Scholar
  55. Kobayashi T, Tahara Y, Takenaka H, Mimura K, Hayashi Y (2007) Na+- and K+-dependent oligomeric interconversion among αβ-protomers, diprotomers and higher oligomers in solubilized Na+/K+-ATPase. J Biochem 142:157–173. doi:10.1093/jb/mvm150 PubMedCrossRefGoogle Scholar
  56. Kong BY, Clarke RJ (2004) Identification of potential regulatory sites of the Na+,K+-ATPase by kinetic analysis. Biochemistry 43:2241–2250. doi:10.1021/bi0355443 PubMedCrossRefGoogle Scholar
  57. Kutchai H, Mahaney JE, Geddis LM, Thomas DD (1994) Hexanol and lidocaine affect the oligomeric state of the Ca-ATPase of sarcoplasmic reticulum. Biochemistry 33:13208–13222. doi:10.1021/bi00249a007 PubMedCrossRefGoogle Scholar
  58. Kutchai H, Geddis LM, Jones LR, Thomas DD (1998) Differential effects of general anesthetics on the quaternary structure of Ca-ATPases of cardiac and skeletal sarcoplasmic reticulum. Biochemistry 37:2410–2421. doi:10.1021/bi9722002 PubMedCrossRefGoogle Scholar
  59. Linnertz H, Urbanova P, Obsil T, Herman P, Amler E, Schoner W (1998) Molecular distance measurements reveal an (αβ)2 dimeric structure of Na+,K+-ATPase. High affinity ATP binding site and K+-activated phosphatase reside on different α-subunits. J Biol Chem 273:28813–28821. doi:10.1074/jbc.273.44.28813 PubMedCrossRefGoogle Scholar
  60. Lüpfert C, Grell E, Pintschovius V, Apell H-J, Cornelius F, Clarke RJ (2001) Rate limitation of the Na+,K+-ATPase pump cycle. Biophys J 81:2069–2081PubMedCrossRefGoogle Scholar
  61. Mahaney JE, Thomas DD, Froehlich JP (2004) The time-dependent distribution of phosphorylated intermediates in native sarcoplasmic reticulum Ca2+-ATPase from skeletal muscle is not compatible with a linear kinetic model. Biochemistry 43:4400–4416. doi:10.1021/bi035068g PubMedCrossRefGoogle Scholar
  62. Mahaney JE, Thomas DD, Farrance IK, Froehlich JP (2008) Intermolecular interactions in the mechanism of skeletal muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA1): evidence for a tri-protomer. Biochemistry 47:13711–13725PubMedCrossRefGoogle Scholar
  63. Martin DW, Sachs JR (1999) Preparation of Na+,K+-ATPase with near maximal specific activity and phosphorylation capacity: evidence that the reaction mechanism involves all of the sites. Biochemistry 38:7485–7497. doi:10.1021/bi983019b PubMedCrossRefGoogle Scholar
  64. Martin DW, Sachs JR (2000) Ligands presumed to label high affinity and low affinity ATP binding sites do not interact in an (αβ)2 diprotomer in duck nasal gland Na+,K+-ATPase, nor do the sites coexist in native enzyme. J Biol Chem 275:24512–24517. doi:10.1074/jbc.M003179200 PubMedCrossRefGoogle Scholar
  65. Martin DW, Maracek J, Scarlata S, Sachs JR (2000) αβ Protomers of Na+,K+-ATPase from microsomes of duck salt gland are mostly monomeric: formation of higher oligomers does not modify molecular activity. Proc Natl Acad Sci USA 97:3195–3200. doi:10.1073/pnas.050558397 PubMedCrossRefGoogle Scholar
  66. Mimura K, Tahara Y, Shinji N, Tokuda E, Takenaka H, Hayashi Y (2008) Isolation of stable (αβ)4-tetraprotomer from Na+/K+-ATPase solubilized in the presence of short-chain fatty acids. Biochemistry 47:6039–6051. doi:10.1021/bi800445f PubMedCrossRefGoogle Scholar
  67. Møller JV, Lind KE, Andersen JP (1980) Enzyme kinetics and substrate stabilization of detergent-solubilized and membranous (Ca2+ + Mg2+)-activated ATPase from sarcoplasmic reticulum. Effect of protein-protein interactions. J Biol Chem 255:1912–1920PubMedGoogle Scholar
  68. Montes MR, González-Lebrero RM, Garrahan PJ, Rossi RC (2004) Quantitative analysis of the interaction between the fluorescent probe eosin and the Na+,K+-ATPase studied through Rb+ occlusion. Biochemistry 43:2062–2069. doi:10.1021/bi0351763 PubMedCrossRefGoogle Scholar
  69. Morth JP, Pedersen BP, Toustrup-Jensen MS, Sørensen TL-M, Petersen J, Andersen JP, Vilsen B, Nissen P (2007) Crystal structure of the sodium-potassium pump. Nature 450:1043–1050. doi:10.1038/nature06419 PubMedCrossRefGoogle Scholar
  70. Nørby JG, Jensen J (1971a) Binding of ATP to brain microsomal ATPase. Determination of the ATP binding capacity and the dissociation constant of the enzyme-ATP complex as a function of K+ concentration. Biochim Biophys Acta 233:104–116. doi:10.1016/0005-2736(71)90362-2 PubMedCrossRefGoogle Scholar
  71. Nørby JG, Jensen J (1971b) Functional significance of the oligomeric structure of the Na,K-pump from radiation inactivation and ligand binding. In: Kaplan JH, De Weer P (eds) The sodium pump: structure, mechanism, and regulation. Rockefeller University Press, New York, pp 173–188Google Scholar
  72. Olesen C, Sørensen TL-M, Nielsen RC, Møller JV, Nissen P (2004) Dephosphorylation of the calcium pump coupled to counterion occlusion. Science 306:2251–2255. doi:10.1126/science.1106289 PubMedCrossRefGoogle Scholar
  73. Olesen C, Picard M, Winther A-ML, Gyrup C, Morth JP, Oxvig C, Møller JV, Nissan P (2007) The structural basis of calcium transport by the calcium pump. Nature 450:1036–1044. doi:10.1038/nature06418 PubMedCrossRefGoogle Scholar
  74. Palladino MJ, Bower JE, Kreber R, Ganetzky B (2003) Neural dysfunction and neurodegeneration in Drosophila Na+/K+-ATPase alpha subunit mutants. J Neurosci 23:1276–1286PubMedGoogle Scholar
  75. Palmgren MG (2001) Plant plasma membrane H+-ATPases: powerhouses for nutrient uptake. Annu Rev Plant Physiol Plant Mol Biol 52:817–845. doi:10.1146/annurev.arplant.52.1.817 PubMedCrossRefGoogle Scholar
  76. Pedersen BP, Buch-Pedersen MJ, Morth JP, Palmgren MG, Nissan P (2007) Crystal structure of the plasma membrane proton pump. Nature 450:1111–1115. doi:10.1038/nature06417 PubMedCrossRefGoogle Scholar
  77. Peluffo RD, Garrahan PJ, Rega AF (1992) Low affinity superphosphorylation of the Na,K-ATPase by ATP. J Biol Chem 267:6596–6601PubMedGoogle Scholar
  78. Peters WHM, Swarts HGP, de Pont JJHHM, Schuurmans Stekhoven FMAH, Bonting SL (1981) (Na+ + K+)ATPase has one functioning phosphorylation site per α subunit. Nature 290:338–339. doi:10.1038/290338a0 PubMedCrossRefGoogle Scholar
  79. Pilotelle-Bunner A, Matthews JM, Cornelius F, Apell H-J, Sebban P, Clarke RJ (2008) ATP binding equilibria of the Na+,K+-ATPase. Biochemistry 47:13103–13114. doi:10.1021/bi801593g PubMedCrossRefGoogle Scholar
  80. Plesner IW (1987) Application of the theory of enzyme subunit interactions to ATP-hydrolyzing enzymes. The case of Na,K-ATPase. Biophys J 51:69–78PubMedCrossRefGoogle Scholar
  81. Plesner IW, Plesner L, Nørby JG, Klodos I (1981) The steady-state kinetic mechanism of ATP hydrolysis catalyzed by membrane-bound (Na+ + K+)-ATPase from ox brain. III. A minimal model. Biochim Biophys Acta 643:483–494. doi:10.1016/0005-2736(81)90090-0 PubMedCrossRefGoogle Scholar
  82. Post RL, Hegyvary C, Kume S (1972) Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J Biol Chem 247:6530–6540PubMedGoogle Scholar
  83. Pratap PR, Palit A, Grassi-Nemeth E, Robinson JD (1996) Kinetics of conformational changes associated with potassium binding to and release from Na+/K+-ATPase. Biochim Biophys Acta 1285:203–211. doi:10.1016/S0005-2736(96)00162-9 PubMedCrossRefGoogle Scholar
  84. Reenstra WW, Bettencourt JD, Forte JG (1988) Kinetic studies of the gastric H,K-ATPase. Evidence for simultaneous binding of ATP and inorganic phosphate. J Biol Chem 263:19618–19625PubMedGoogle Scholar
  85. Repke KRH, Schön R (1973) Flip-flop model of (NaK)-ATPase function. Acta Biol Med Ger 31:K19–K30PubMedGoogle Scholar
  86. Roberts G, Beaugé L (1997) Complex ATP-activation kinetics of plant H+-transporting ATPase may or may not require two substrate sites. Eur J Biochem 246:228–232. doi:10.1111/j.1432-033.1997.00228.x PubMedCrossRefGoogle Scholar
  87. Scheiner-Bobis G (2002) The sodium pump. Its molecular properties and mechanics of ion transport. Eur J Biochem 269:2424–2433. doi:10.1046/j.1432-1033.2002.02909.x PubMedCrossRefGoogle Scholar
  88. Scheiner-Bobis G, Fahlbusch K, Schoner W (1987) Demonstration of cooperating α subunits in working (Na+ + K+)-ATPase by the use of the MgATP complex analogue cobalt tetraammine ATP. Eur J Biochem 168:123–131. doi:10.1111/j.1432-1033.1987.tb13396.x PubMedCrossRefGoogle Scholar
  89. Schneeberger A, Apell HJ (2001) Ion selectivity of the cytoplasmic binding sites of the Na,K-ATPase: II. Competition of various cations. J Membr Biol 179:263–273. doi:10.1007/s002320010051 PubMedCrossRefGoogle Scholar
  90. Schoner W, Mertens W, Helms M, Fortes G (1998) Binding of the Co(NH3)4 derivative of (2′)3′-O-[N-methyl-anthraniloyl]-ATP to the E2ATP site of Na+/K+-transporting ATPase lowers the conformational flexibility of its E1ATP site. Eur J Biochem 253:245–250. doi:10.1046/j.1432-1327.1998.2530245.x PubMedCrossRefGoogle Scholar
  91. Shin JM, Vagin O, Munson K, Sachs G (2004) Gastric H+,K+-ATPase. In: Futai F, Wada Y, Kaplan JH (eds) Handbook of ATPases. Biochemistry, cell biology, pathophysiology. Wiley-VCH, Weinheim, pp 179–209Google Scholar
  92. Shin JM, Grundler G, Senn-Bilfinger J, Simon WA, Sachs G (2005) Functional consequences of the oligomeric form of the membrane-bound gastric H,K-ATPase. Biochemistry 44:16321–16332. doi:10.1021/bi051342q PubMedCrossRefGoogle Scholar
  93. Skou JC (1957) The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim Biophys Acta 23:394–401. doi:10.1016/0006-3002(57)90343-8 PubMedCrossRefGoogle Scholar
  94. Skriver E, Maunsbach AB, Hebert H, Scheiner-Bobis G, Schoner W (1989) Two-dimensional crystalline arrays of Na,K-ATPase with new subunit interactions induced by cobalt-tetrammine-ATP. J Ultrastruct Mol Struct Res 102:189–195. doi:10.1016/0889-1605(89)90013-X PubMedCrossRefGoogle Scholar
  95. Sørensen TL-M, Møller JV, Nissen P (2004) Phosphoryl transfer and calcium ion occlusion in the calcium pump. Science 304:1672–1675. doi:10.1126/science.1099366 PubMedCrossRefGoogle Scholar
  96. Stein WD, Lieb WR, Karlish SJD, Eilam Y (1973) A model for active transport of sodium and potassium ions as mediated by a tetrameric enzyme. Proc Natl Acad Sci USA 70:275–278. doi:10.1073/pnas.70.1.275 PubMedCrossRefGoogle Scholar
  97. Steinberg M, Karlish SJD (1989) Studies of conformational changes in Na,K-ATPase labeled with 5-iodoacetamidofluorescein. J Biol Chem 264:2726–2734PubMedGoogle Scholar
  98. Stürmer W, Bühler R, Apell H-J, Läuger P (1991) Charge translocation by the Na,K-pump: II. Ion binding and release at the extracellular face. J Membr Biol 121:163–176. doi:10.1007/BF01870530 PubMedCrossRefGoogle Scholar
  99. Taniguchi K, Kaya S, Abe K, Mårdh S (2001) The oligomeric nature of Na/K-transport ATPase. J Biochem 129:335–342PubMedGoogle Scholar
  100. Tanoue K, Kaya S, Hayashi Y, Abe K, Imagawa T, Taniguchi K, Sakaguchi K (2006) New evidence for ATP binding induced catalytic subunit interactions in pig kidney Na/K-ATPase. J Biochem 140:599–607. doi:10.1093/jb/mvj191 PubMedCrossRefGoogle Scholar
  101. Thoenges D, Schoner W (1997) 2′-O-Dansyl analogs of ATP bind with high affinity to the low affinity ATP site of Na+/K+-ATPase and reveal the interaction of two ATP sites during catalysis. J Biol Chem 272:16315–16321. doi:10.1074/jbc.272.26.16315 PubMedCrossRefGoogle Scholar
  102. Toyoshima C (2008) Structural aspects of ion pumping by Ca2+-ATPase of sarcoplasmic reticulum. Arch Biochem Biophys 476:3–11. doi:10.1016/ PubMedCrossRefGoogle Scholar
  103. Toyoshima C, Mizutani T (2004) Crystal structure of the calcium pump with a bound ATP analogue. Nature 430:529–535. doi:10.1038/nature02680 PubMedCrossRefGoogle Scholar
  104. Toyoshima C, Nomura H (2002) Structural changes in the calcium pump accompanying the dissociation of calcium. Nature 418:605–611. doi:10.1038/nature00944 PubMedCrossRefGoogle Scholar
  105. Toyoshima C, Nakasako M, Nomura H, Ogawa H (2000) Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution. Nature 405:647–655. doi:10.1038/35015017 PubMedCrossRefGoogle Scholar
  106. Toyoshima C, Nomura H, Tsuda T (2004) Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues. Nature 432:361–368. doi:10.1038/nature02981 PubMedCrossRefGoogle Scholar
  107. Tsuda T, Kaya S, Yokoyama T, Hayashi Y, Taniguchi K (1998) ATP and acetyl phosphate induces molecular events near the ATP binding site and the membrane domain of Na+,K+-ATPase. The tetrameric nature of the enzyme. J Biol Chem 273:24339–24345. doi:10.1074/jbc.273.38.24339 PubMedCrossRefGoogle Scholar
  108. Vilsen B, Andersen JP, Petersen J, Jørgensen PL (1987) Occlusion of 22Na+ and 86Rb+ in membrane-bound and soluble protomeric αβ-units of Na,K-ATPase. J Biol Chem 262:10511–10517PubMedGoogle Scholar
  109. Ward DG, Cavieres JD (1996) Binding of 2′(3′)-O-(2, 4, 6-trinitrophenyl)ADP to soluble αβ protomers of Na,K-ATPase modified with fluorescein isothiocyanate. Evidence for two distinct nucleotide sites. J Biol Chem 271:12317–12321. doi:10.1074/jbc.271.21.12317 PubMedCrossRefGoogle Scholar
  110. Ward DG, Cavieres JD (2003) Inactivation of Na,K-ATPase following Co(NH3)4ATP binding at a low affinity site in the protomeric enzyme unit. J Biol Chem 278:14688–14697. doi:10.1074/jbc.M211128200 PubMedCrossRefGoogle Scholar
  111. Ward DG, Taylor M, Lilley KS, Cavieres JD (2006) TNP-8N3-ADP photoaffinity labeling of two Na,K-ATPase sequences under separate Na+ plus K+ control. Biochemistry 45:3460–3471. doi:10.1021/bi051927k PubMedCrossRefGoogle Scholar
  112. Yokoyama T, Kaya S, Abe K, Taniguchi K, Katoh T, Yazawa M, Hayashi Y, Mårdh S (1999) Acid-labile ATP and/or ADP/Pi binding to the tetraprotomeric form of Na/K-ATPase accompanying catalytic phosphorylation-dephosphorylation cycle. J Biol Chem 274:31792–31796. doi:10.1074/jbc.274.45.31792 PubMedCrossRefGoogle Scholar

Copyright information

© European Biophysical Societies' Association 2009

Authors and Affiliations

  1. 1.School of ChemistryUniversity of SydneySydneyAustralia

Personalised recommendations