Article
Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff.
Genetics - 6 Nov 2024
Boyle Gabriel E, Sitko Katherine A, Galloway Jared G, Haddox Hugh K, Bianchi Aisha Haley, Dixon Ajeya, Wheelock Melinda K, Vandi Allyssa J, Wang Ziyu R, Thomson Raine E S, Garge Riddhiman K, Rettie Allan E, Rubin Alan F, Geck Renee C, Gillam Elizabeth M J, DeWitt William S, Matsen Frederick A, Fowler Douglas M
Abstract excerpt
The cytochrome P450s enzyme family metabolizes ∼80% of small molecule drugs. Variants in cytochrome P450s can substantially alter drug metabolism, leading to improper dosing and severe adverse drug reactions. Due to low sequence conservation, predicting variant effects across cytochrome P450s is challenging. Even closely related cytochrome P450s like CYP2C9 and CYP2C19, which share 92% amino acid sequence...
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