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A model for interfacial activation in lipases from the structure of a fungal lipase-inhibitor complex

Nature volume 351, pages 491–494 (1991)Cite this article

Abstract

LIPASES are hydrolytic enzymes which break down triacylglycerides into free fatty acids and glycerols. They have been classified as serine hydrolases owing to their inhibition by diethyl p-nitrophenyl phosphate1. Lipase activity is greatly increased at the lipid-water interface2,3, a phenomenon known as interfacial activation. X-ray analysis has revealed the atomic structures of two triacylglycerol lipases, unrelated in sequence: the human pancreatic lipase (hPL)4, and an enzyme isolated from the fungus Rhizomucor (formerly Mucor) miehei5 (RmL). In both enzymes the active centres contain structurally analogous Asp-His-Ser triads (characteristic of serine proteinases), which are buried completely beneath a short helical segment, or 'lid'. Here we present the crystal structure (at 3 Å resolution) of a complex of R. miehei lipase with n-hexylphosphonate ethyl ester in which the enzyme's active site is exposed by the movement of the helical lid. This movement also increases the nonpolarity of the surface surrounding the catalytic site. We propose that the structure of the enzyme in this complex is equivalent to the activated state generated by the oil–water interface.

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Author notes

  1. U. Derewenda & Z. S. Derewenda

    Present address: MRC Group in Protein Structure and Function, Department of Biochemistry, 474 Medical Sciences Building, University of Alberta, Edmonton, Canada, T6G 2H7

  2. F. Bjorkling, B. Huge-Jensen, S. A. Patkar and L. Thim: Novo-Nordisk A/S, Novo Alle, DK-2880 Bagsvaerd, Copenhagen, Denmark

Authors and Affiliations

  1. Department of Chemistry, University of York, Heslington, York, YO1 5DD, UK

    A. M. Brzozowski, U. Derewenda, Z. S. Derewenda, G. G. Dodson, D. M. Lawson, J. P. Turkenburg, F. Bjorkling, B. Huge-Jensen, S. A. Patkar & L. Thim

  2. Department of Crystallography, Institute of Chemistry, University of Lodz, 91416, Lodz, Poland

    A. M. Brzozowski

Authors
  1. A. M. Brzozowski
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  9. S. A. Patkar
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Brzozowski, A., Derewenda, U., Derewenda, Z. et al. A model for interfacial activation in lipases from the structure of a fungal lipase-inhibitor complex. Nature 351, 491–494 (1991). https://doi.org/10.1038/351491a0

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