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Roussel, A ; Miled, N ; Berti-Dupuis, L ; Riviere, M ; Spinelli, S ; Berna, P ; Gruber, V ; Verger, R ; Cambillau, C

Crystal structure of the open form of dog gastric lipase in complex with a phosphonate inhibitor

Journal of Biological Chemistry 277 (3) 2266-2274

par Administrateur - publié le

Abstract :

Fat digestion in humans and some mammals such as dogs requires the successive intervention of two lipases : gastric lipase, which is stable and active despite the highly acidic stomach environment, followed by the classical pancreatic lipase secreted into the duodenum. We previously solved the structure of recombinant human gastric lipase (HGL) at 3.0-Angstrom resolution in its closed form ; this was the first structure to be described within the mammalian acid lipase family. Here we report on the open structure of the recombinant dog gastric lipase (r-DGL) at 2.7-Angstrom resolution in complex with the undecylbutyl (C11Y4) phosphonate inhibitor. HGL and r-DGL show 85.7% amino acid sequence identity, which makes it relevant to compare the forms from two different species.