THE Ser-His-Asp triad is a well known structural feature of the serine proteases. It has also been directly observed in the catalytic sites of two Upases, whose high-resolution three-dimensional structures have been determined1,2. Lipases show a wide variety of sizes, substrate and positional specificities, and catalytic rates3. They achieve maximal catalytic rates at oil–water interfaces. The fungus Geotrichum candidum produces several different forms of Upases, two of which have been purified to homogeneity4,5. Two lipase genes have been identified, cloned and sequenced6,7. Both code for proteins of 544 amino acids with a total relative molecular mass of about 60,000 (Mr 60K). The two forms are 86% identical. Their isoelectric points differ slightly, being between 4.3 and 4.6. About 7% of the total Mr is carbohydrate. Until now, only a low resolution structure of GCL has been reported8, but no high resolution structure has followed. We now report the three-dimensional structure of a lipase from G. candidum (GCL) at 2.2 Å resolution. Unlike the other Upases and serine proteases, the catalytic triad of GCL is Ser-His-Glu, with glutamic acid replacing the usual aspartate. Although the sequence similarity with the other two Upases is limited to the region near the active-site serine, there is some similarity in their three-dimensional structures. The GCL is also an α/β protein with a central mixed β sheet whose topology is similar to that of the N-terminal domain of human pancreatic lipase. As in the other lipases1,2, the catalytic site is buried under surface loops. Sequence comparisons with proteins from the cholinesterase family suggest that they also contain the Ser-His-Glu triad.
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Schrag, J., Li, Y., Wu, S. et al. Ser-His-Glu triad forms the catalytic site of the lipase from Geotrichum candidum. Nature 351, 761–764 (1991). https://doi.org/10.1038/351761a0
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