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Structure of human pancreatic lipase


PANCREATIC lipase (triacylglycerol acyl hydrolase) fulfills a key function in dietary fat absorption by hydrolysing triglycerides into diglycerides and subsequently into monoglycerides and free fatty acids. We have determined the three-dimensional structure of the human enzyme, a single-chain glycoprotein of 449 amino acids, by X-ray crystallography and established its primary structure by sequencing complementary DNA clones. Enzymatic activity is lost after chemical modification of Ser 152 in the porcine enzyme1,2, indicating that this residue is essential in catalysis, but other data3,4 are more consistent with a function in interfacial recogni-tion. Our structural results are evidence that Ser 152 is the nucleophilic residue essential for catalysis. It is located in the larger N-terminal domain at the C-terminal edge of a doubly wound parallel β-sheet and is part of an Asp-His-Ser triad, which is chemically analogous to, but structurally different from, that in the serine proteases. This putative hydrolytic site is covered by a surface loop and is therefore inaccessible to solvent. Interfacial activation, a characteristic property of lipolytic enzymes acting on water-insoluble substrates at water-lipid interfaces, probably involves a reorientation of this flap, not only in pancreatic lipases but also in the homologous hepatic and lipoprotein lipases.

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  1. Maylié, M. F., Charles, M. & Desnuelle, P. Biochim. biophys. Acta 276, 162–175 (1972).

    Article  Google Scholar 

  2. Guidoni, A., Benkouka, F., De Caro, J. & Rovery, M. Biochim. biophys. Acta 660, 148–150 (1981).

    Article  CAS  Google Scholar 

  3. Chapus, C. & Sémériva, M. Biochemistry 15, 4988–4991 (1976).

    Article  CAS  Google Scholar 

  4. Chapus, C., Sémériva, M., Bovier-Lapierre, C. & Desnuelle, P. Biochemistry 15, 4980–4987 (1976).

    Article  CAS  Google Scholar 

  5. De Caro, J. et al. Biochim. biophys. Acta 671, 129–138 (1981).

    Article  CAS  Google Scholar 

  6. Kerfélec, B., LaForge, K. S., Puigserver, A. & Scheele, G. Pancreas 1, 430–437 (1986).

    Article  Google Scholar 

  7. Sternby, B. & Borgström, B. Comp. biochem. Physiol. 688, 15–18 (1981).

    Google Scholar 

  8. Bricogne, G. Acta crystallogr. A32, 832–847 (1976).

    Article  ADS  CAS  Google Scholar 

  9. Jones, T. A. J. appl. Crystallogr. 11, 268–272 (1978).

    Article  CAS  Google Scholar 

  10. Brünger, A. T., Kuriyan, J. & Karplus, M. Science 235, 458–460 (1987).

    Article  ADS  Google Scholar 

  11. Richardson, J. S. Meth. Enzym. 115, 341–358 (1985).

    Article  CAS  Google Scholar 

  12. Richardson, J. S. Proc. natn. Acad. Sci. U.S.A. 73, 2619–2623 (1976).

    Article  ADS  CAS  Google Scholar 

  13. Sternberg, M. J. E. & Thornton, J. M. J. molec. Biol. 110, 269–283 (1977).

    Article  CAS  Google Scholar 

  14. Chapus, C., Rovery, M., Sarda, L. & Verger, R. Biochimie 70, 1223–1234 (1988).

    Article  CAS  Google Scholar 

  15. Datta, S. et al. J. biol. Chem. 263, 1107–1110 (1988).

    CAS  PubMed  Google Scholar 

  16. Rotanova, T. V., Klaus, R., Ivanova, A. G., Ginodman, L. & Antonov, V. K. Bioorg. Khim. 2, 837–845 (1976).

    CAS  Google Scholar 

  17. Garner, C. W. J. biol. Chem. 255, 5064–5068 (1980).

    CAS  PubMed  Google Scholar 

  18. De Caro, J. D., Rouimi, P. & Rovery, M. Eur. J. Biochem. 158, 601–607 (1986).

    Article  CAS  Google Scholar 

  19. De Caro, J. D., Chautan, M. P., Rouimi, P. & Rovery, M. 70, 1785–1790 (1988).

  20. Bengtsson-Olivecrona, G., Olivecrona, T. & Jönvall, H. Eur. J. Biochem. 161, 281–288 (1986).

    Article  CAS  Google Scholar 

  21. Bengtsson, G. & Olivecrona, T. Eur. J. Biochem. 113, 547–554 (1981).

    Article  CAS  Google Scholar 

  22. Persson, B., Bengtsson-Olivecrona, G., Enerbäck, S., Olivecrona, T. & Jörnvall, H. Eur. J. Biochem. 179, 39–45 (1989).

    Article  CAS  Google Scholar 

  23. Kabsch, W. J. appl. Crystallogr. 21, 916–924 (1988).

    Article  CAS  Google Scholar 

  24. Dickerson, R. E., Weinzierl, J. E. & Palmer, R. A. Acta crystallogr. B24, 997–1001 (1968).

    Article  Google Scholar 

  25. Kabsch, W. & Sander, C. Biopolymers 22, 2577–2637 (1983).

    Article  CAS  Google Scholar 

  26. Bode, W. & Schwager, P. J. molec. Biol. 98, 693–717 (1975).

    Article  CAS  Google Scholar 

  27. Bernstein, F. C. et al. J. molec. Biol. 112, 535–543 (1977).

    Article  CAS  Google Scholar 

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Winkler, F., D'Arcy, A. & Hunziker, W. Structure of human pancreatic lipase. Nature 343, 771–774 (1990).

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