Active site breathing of the human RNA demethylase Alkbh5 revealed by solution NMR and accelerated Molecular Dynamics simulations

AlkB homologue 5 (Alkbh5) is one of nine members of the AlkB family, which are non-heme Fe2+/α-ketoglutarate (αKG)-dependent dioxygenases that catalyze the oxidative demethylation of modified nucleotides and amino acids. Alkbh5 is highly selective for the N6-methyladenosine (m6A) modification, an epigenetic mark that has spawned significant biological and pharmacological interest, due to its involvement in important physiological processes, such as carcinogenesis and stem-cell differentiation. Herein, we investigate the structure and dynamics of human Alkbh5 in solution.

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