Journal of Bioenergetics and Biomembranes

, Volume 21, Issue 5, pp 573–588 | Cite as

Functional domains of the gastric HK ATPase

  • G. Sachs
  • K. Munson
  • V. N. Balaji
  • D. Aures-Fischer
  • S. J. Hersey
  • K. Hall


The gastric H+ + K+ ATPase is a member of the phosphorylating class of transport ATPase. Based on sequence homologies and CHO content, there may be ab subunit associated with the catalytic subunit of the H+ + K+ ATPase. Its function, if present, is unknown. The pump catalyzes a stoichiometric exchange of H+ for K+, but is also able to transport Na+ in the forward direction. This suggests that the transport step involves hydronium rather than protons. The initial binding site is likely to contain a histidine residue to account for the high affinity of the cellular site. The extracellular site probably lacks this histidine, so that a low affinity for hydronium allows release into a solution of pH 0.8. Labelling with positively charge, luminally reactive reagents that block ATPase and pump activity has shown that a region containing H5 and H6 and the intervening luminal loop is involved in necessary conformational changes for normal pump activity. The calculated structure of this loop shows the presence of ana helical,b turn, andb strand sector, with negative charges close to the membrane domain. This sector provides a possible site of interaction of drugs with the H+ + K+ ATPase, and may be part of the K+ pathway in the enzyme.

Key Words

Gastric H+ transport ATPase omeprazole K+ site 


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  1. Alawqati, Q. (1986)Annu. Rev. Cell. Biol. 2, 179–199.Google Scholar
  2. Boyer, P. D. (1988)Trends Biochem. Sci. 12, 3–7.Google Scholar
  3. Brooker, R. J., and Slayman, C. W. (1983)J. Biol. Chem. 258, 222–226.Google Scholar
  4. Brown, T. A., Horowitz, B., Miller, R. P., Mcdonough, A. A., and Farley, R. A. (1987)Biochem. Biophys. Acta 912, 244–253.Google Scholar
  5. Caplan, M. J., Baron, R., Neff, L., Shull, G., and Forbush, B. R. (1989)J. Cell. Biol. 107, 783A.Google Scholar
  6. Collins, J. H., and Leszyk, J. (1987)Biochemistry 26, 8665–8668.Google Scholar
  7. Fendler, K., Van der Hijden, H., Nael, G., Depont, J. J., and Bamberg, E. (1988)Prog. Clin. Biol. Res. 268, 501–510.Google Scholar
  8. Forgac, M., and Cantley, L. (1984)J. Biol. Chem. 259, 8101–8105.Google Scholar
  9. Ganser, A. L., and Forte, J. G. (1973)Biochim. Biophys. Acta 307, 169–180.Google Scholar
  10. Geering, K., Meyer, D. I., Paccolat, M. P., Kraehenbul, J. P., and Rossier, B. C. (1985)J. Biol. Chem. 260, 5154–5160.Google Scholar
  11. Goldshlegger, R., Karlish, S. J. D., Rephaeli, A., and Stein, W. D. (1987)J. Physiol. 287, 331–355.Google Scholar
  12. Hall, C. C., and Ruochi, A. E. (1980)Proc. Natl. Acad. Sci. USA 77, 4529–4533.Google Scholar
  13. Hall, K., Perez, G., Anderson, D., Kaplan, J., Hersey, S. J., and Sachs, G. (1989a),Faseb J. 3, A873.Google Scholar
  14. Hall, K., Perez, G., Anderson, D., Kaplan, J. H., Hersey, S. J., and Sachs, G. (1989b)Biochemistry, in press.Google Scholar
  15. Hersey, S. J., Steiner, L., Mendlein, J., Rabon, E., and Sachs, G. (1988)Biochem. Biophys. Acta 956, 49–57.Google Scholar
  16. Jorgensen, P. L., and Andersen, J. P. (1988)J. Membr. Biol. 103, 95–120.Google Scholar
  17. Karlish, S. J. D., and Kempner, E. S. (1984)Biochem. Biophys. Acta 776, 288–298.Google Scholar
  18. Keeling, D. J. Fallowfield, C., Lawrie, K. M. W., Saunders, D., Richardson, S., and Ife, R. J. (1988a)J. Biol. Chem. 264, 5552–5558.Google Scholar
  19. Keeling, D. J., Taylor, A. G., and Schudt, C. (1989b)J. Biol. Chem. 264, 5545–5551.Google Scholar
  20. Lorentzon, P., Eklundh, B., Brandstrom, A., and Wallmark, B. (1985)Biochem. Biophys. Acta 817, 25–32.Google Scholar
  21. Lorentzon, P., Jackson, R. J., Wallmark, B., and Sachs, G. (1987)Biochem. Biophys. Acta 897, 41–51.Google Scholar
  22. Lorentzon, P., Sachs, G., and Wallmark, B. (1988)J. Biol. Chem. 263, 10705–10710.Google Scholar
  23. Maeda, M., Ishizaki, J., and Futai, M. (1988a)Biochem. Biophys. Res. Commun. 157, 203–209.Google Scholar
  24. Maeda, M., Tagaya, M., and Futai, M. (1988b)J. Biol. Chem. 263, 3652–3656.Google Scholar
  25. Munson, K. B., and Sachs, G. (1988)Biochemistry 27, 3932–3938.Google Scholar
  26. Okamoto, C., Reenstra, W. W., Li, W., and Forte, J. G. (1989)J. Cell. Biol. 107, 125a.Google Scholar
  27. Ovchinnikov, Y. A. (1987)Trends Biochem. Sci. 12, 434–438.Google Scholar
  28. Pederson, P. L. (1983)Annu. Rev. Biochem. 52, 801–824.Google Scholar
  29. Polvani, C., Sachs, G., and Blostein, R. (1989)Biophys. J. 55, 337A.Google Scholar
  30. Rabon, E. C., and Bassilian, S. (1989)Biochemistry, in press.Google Scholar
  31. Rabon, E. C., Gunther, R. D., Bassilian, S., and Kempner, E. S. (1988)J. Biol. Chem. 263, 16189–16194.Google Scholar
  32. Reenstra, W. W., Bettencourt, J. D., and Forte, J. G. (1988)J. Biol. Chem. 263, 19618–19625.Google Scholar
  33. Saccomani, G., Barcellona, M. L., Rabon, E., and Sachs, G. (1980) inHydrogen Ion Transport in Epithelia (Schulz, I., Sachs, G., Forte, J. G., and Ulrich, K. J., eds.), Elsevier, Amsterdam, pp. 175–183.Google Scholar
  34. Saccomani, G., Barcellona, M. L., and Sachs, G. (1981)J. Biol. Chem. 256, 12405–12410.Google Scholar
  35. Sachs, G., Chang, H. H., Rabon, E., Schackmann, R., Lewin, M., and Saccomani, G. (1976)J. Biol. Chem. 251, 7690–7698.Google Scholar
  36. Sachs, G., Carlsson, E., Lindberg, P., and Wallmark, B. (1988)Annu. Rev. Pharmacol. Toxicol. 28, 269–284.Google Scholar
  37. Sachs, G., Hall, K., Munson, K., Aures-Fischer, D., Anderson, D. N., Balaji, V. N., and Hersey, S. J., inPumps, Carriers, and Channels (Keeling, D. J., and Rink, T. J., eds.), Academic Press, in press.Google Scholar
  38. Serrano, R., Kielland-Brandt, M. C., and Fink, G. R. (1986)Nature (London)219, 689–693.Google Scholar
  39. Shull, G. E., and Lingrel, J. B. (1986)J. Biol. Chem. 261, 16788–16791.Google Scholar
  40. Solioz, M., Mathews, S., and Furst, P. (1987)J. Biol. Chem. 262, 7458–7462.Google Scholar
  41. Spenney, J. G., Saccomani, G., Spitzer, H. L., Tomana, M., and Sachs, G. (1974)Arch. Biochem. Biophys. 161, 456–471.Google Scholar
  42. Tai, M. M., Im, W. B., Davis, J. P., Blakeman, D. P., Zurcher Neely, H. A., and Heinrikson, R. L., (1989)Biochemistry 28, 3183–3187.Google Scholar
  43. Wallmark, B. Stewart, H. B. Rabon, E., Saccomani, G., and Sachs, G. (1980)J. Biol. Chem. 255, 5313–5319.Google Scholar
  44. Wallmark, B., Briving, C., Fryklund, J., Munson, K., Jackson, R., Mendlein, J., Rabon, E., and Sachs, G. (1987)J. Biol. Chem. 262, 2077–2084.Google Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • G. Sachs
    • 1
  • K. Munson
    • 1
  • V. N. Balaji
    • 1
  • D. Aures-Fischer
    • 1
  • S. J. Hersey
    • 1
  • K. Hall
    • 1
  1. 1.University of California at Los Angeles and Wadsworth VALos Angeles

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