6KSM

Staphylococcus aureus lipase -Orlistat complex

6KSM の概要

• エントリーDOI: 10.2210/pdb6ksm/pdb
• 関連するPDBエントリー: 6KSI 6KSL
• 分子名称: Lipase 2, ZINC ION, CALCIUM ION, ... (8 entities in total)
• 機能のキーワード: orlistat binding, hydrolase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94095.22

構造登録者

Kitadokoro, K.,Tanaka, M.,Kamitani, S. (登録日: 2019-08-24, 公開日: 2020-04-08, 最終更新日: 2023-11-22)

主引用文献

Kitadokoro, K.,Tanaka, M.,Hikima, T.,Okuno, Y.,Yamamoto, M.,Kamitani, S.
Crystal structure of pathogenic Staphylococcus aureus lipase complex with the anti-obesity drug orlistat.
Sci Rep, 10:5469-5469, 2020

PubMed Abstract: Staphylococcus 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.

PubMed: 32214208
DOI: 10.1038/s41598-020-62427-8

実験手法

X-RAY DIFFRACTION (2.23 Å)