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Regulation of Pancreatic Phospholipase A2 Activity by Different Lipid-Water Interfaces

  • M. C. E. van Dam-Mieras
  • A. J. Slotboom
  • H. M. Verheij
  • R. Verger
  • G. H. de Haas
Part of the Nobel Foundation Symposia book series (NOFS, volume 34)

Summary

Pancreatic phospholipase A2 interacts with lipid-water interfaces by means of a specific region, the Interface Recognition Site (IRS), which most probably penetrates to a certain extent into the hydrophobic interior of the lipid phase. This process causes a dramatic increase in the rate of hydrolysis. The IRS embraces at least the rather apolar N-terminal sequence of the polypeptide chain: Ala. Leu. Trp. Gln. Phe. Arg. Ser. Met and its most effective configuration seems to be stabilised by an ionpair between the \(\alpha -\overset{+}{\mathop{N}}\,{{H}_{3}}\) group of the N-terminal amino acid Ala and a buried carboxylate function.

Using a series of specifically modified phospholipases,in which the native N-terminal amino acid L-Ala has been deleted or substituted by other amino acids, the properties of the IRS were compared by spectroscopic techniques and monolayer kinetics..

Substitution of L-Ala by Gly or ?-Ala does not seriously impede the penetrating properties of the enzyme. Chain elongation, chain shortening or even replacement of L-Ala by D-Ala, however, weakens the IRS in such a manner, that penetration of the relatively close-packed micelles becomes impossible. These enzymes still interact with monomolecular surface films up to well-defined surface pressures.

Keywords

Surface Pressure Salt Bridge Pyroglutamic Acid Pancreatic Phospholipase Single Tryptophan Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1).
    G.H. de Haas, A.J. Slotboom, P.P.M. Bonsen, L.L.M. van Deenen, S. Maroux, A. Puigserver and P. Desnuelle, Biochim. Biophys. Acta, 221 (1970) 31.Google Scholar
  2. 2).
    G.H. de Haas, A.J. Slotboom, P.P.M. Bonsen, W. Nieuwenhuizen, L.L.M. van Deenen, S. Maroux, V. Dlouha, P. Desnuelle, Biochim. Biophys. Acta, 221 (1970) 54.Google Scholar
  3. 3).
    G.H. de Haas, N. Postema, W. Nieuwenhuizen and L.L.A. van Deenen, Biochim. Biophys. Acta, 159 (1968) 103.Google Scholar
  4. 4).
    R. Verger, M.C.E. Mieras and G.H. de Haas, J. Biol. Chem., 248 (1973) 4023.PubMedGoogle Scholar
  5. 5).
    W.A. Pieterson, J.C. Vidal, J.J. Volwerk and G.H. de Haas Biochemistry, 13 (1974) 1455.Google Scholar
  6. 6).
    R.D. Hershberg, G.H. Reed, A.J. Slotboom and G.H. de Haas, Biochemistry, 15 (1976), accepted for publication.Google Scholar
  7. 7).
    J.P. Abita, M. Lazdunski, P.P.M. Bonsen, W.A. Pieterson and G.H. de Haas, Eur. J. Biochem., 30 (1972) 37.PubMedCrossRefGoogle Scholar
  8. 8).
    M.C.E. van Dam-Mieras, A.J. Slotboom, W.A. Pieterson and G.H. de Haas, Biochemistry, 14 (1975) 5387.PubMedCrossRefGoogle Scholar
  9. 9).
    R. Verger and G.H. de Haas, Annual Review of Biophysics and Bioengineering, 5 (1976) 77.PubMedCrossRefGoogle Scholar
  10. 10).
    F.M. van Wezel, A.J. Slotboom and G.H. de Haas, manuscript in preparation.Google Scholar
  11. 11).
    A.J. Slotboom and G.H. de Haas, Biochemistry, 14 (1975) 5394.CrossRefGoogle Scholar
  12. 12).
    L.H.M. Janssen, S.H. de Bruin and G.H. de Haas, Eur. J. Biochem., 28 (1972) 156.PubMedCrossRefGoogle Scholar
  13. 13).
    A. Evenberg, H. Meyer, H.M. Verheij and G.H. de Haas, Eur. J. Biochem., submitted for publication.Google Scholar
  14. 14).
    J.J. Volwerk, W.A. Pieterson and G.H. de Haas, Biochemistry, 13 (1974) 1446.CrossRefGoogle Scholar
  15. 15).
    W.A. Pieterson, J.J. Volwerk and G.H. de Haas, Biochemistry, 13 (1974) 1439.CrossRefGoogle Scholar
  16. 16).
    G.H. de Haas, P.P.M. Bonsen, W.A. Pieterson and L.L.M. van Deenen, Biochim. Biophys. Acta,. 239 (1971) 252.Google Scholar
  17. 17).
    W. Nieuwenhuizen, H. Kunze and G.H. de Haas, Methods Enzymol. 32B (1974) 147.CrossRefGoogle Scholar
  18. 18).
    R. Verger, J. Rietsch, M.C.E. van Dam-Mieras and G.H. de Haas, J. Biol. Chem., 251 (1976), accepted for publication.Google Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • M. C. E. van Dam-Mieras
    • 1
  • A. J. Slotboom
    • 1
  • H. M. Verheij
    • 1
  • R. Verger
    • 2
  • G. H. de Haas
    • 1
  1. 1.Laboratory of Biochemistry State University of Utrecht, Transitorium 3University Centre “De Uithof”UtrechtThe Netherlands
  2. 2.Centre de Biochimie et de Biologie MoleculaireMarseille, Cédex 2France

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