Activation of aldo-keto reductase family member 1B14 (AKR1B14) by bile acids: Activation mechanism and bile acid-binding site

► AKR1B14 metabolizes cytotoxic aldehydes and prostaglandin H2. ► We find that bile acids significantly activate the activity of AKR1B14. ► Bile acid accelerates the NADP+ dissociation, rate-limiting step of the catalysis. ► Bile acid interacts with His269 and facilitates the NADP+ release.