Project Grant R01DK148388

The National Institute of Diabetes and Digestive and Kidney Diseases awarded The Leland Stanford Junior University $2,404,071 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to conduct biochemical and structural studies of phosphotriesterase-related (PTER), an orphan mammalian metabolic enzyme linked to body mass index and obesity.

The award funds research to elucidate the structural basis for PTER catalysis and substrate specificity, determine the requirements for small-molecule inhibition of PTER enzyme activity, and develop potent and selective inhibitors. The recipient has established that N-acetyltaurine is a physiologic substrate for PTER and has identified a direct functional link between PTER, N-acetyltaurine, and obesity. The research will test the central hypothesis that PTER is a mammalian amidohydrolase that catalyzes catabolism of multiple N-acetyl metabolite substrates, with the goal of identifying compounds suitable for therapeutic targeting. Preliminary co-crystal structures of the first eukaryotic PTER in complex with ligands will inform mutagenesis approaches to test catalytic mechanisms, and preliminary studies have already identified a potent small-molecule PTER inhibitor for further optimization.

The project runs from September 1, 2026, through August 31, 2030, with performance taking place in Palo Alto, California. This is a Project Grant assistance type.