Kengo Kitadokoro, Mutsumi Tanaka, Takaaki Hikima, Yukiko Okuno, Masaki Yamamoto, Shigeki Kamitani
Scientific reports 2020 Mar 25Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor and may be a therapeutic target for infectious diseases. Herein, we determined the 3D structure of native SAL, the mutated S116A inactive form, and the inhibitor complex using the anti-obesity drug orlistat to aid in drug development. The determined crystal structures showed a typical α/β hydrolase motif with a dimeric form. Fatty acids bound near the active site in native SAL and inactive S116A mutant structures. We found that orlistat potently inhibits SAL activity, and it covalently bound to the catalytic Ser116 residue. This is the first report detailing orlistat-lipase binding. It provides structure-based information on the production of potent anti-SAL drugs and lipase inhibitors. These results also indicated that orlistat can be repositioned to treat bacterial diseases.
Kengo Kitadokoro, Mutsumi Tanaka, Takaaki Hikima, Yukiko Okuno, Masaki Yamamoto, Shigeki Kamitani. Crystal structure of pathogenic Staphylococcus aureus lipase complex with the anti-obesity drug orlistat. Scientific reports. 2020 Mar 25;10(1):5469
PMID: 32214208
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