THE STORY
This video depicts how preclinical candidate CMX410, a drug containing Sulfur Fluoride Exchange (SuFEx) reactive warhead, acts to inhibit thioesterase domain (TE) of polyketide synthase 13 (Pks13) of M.tuberculosis. After binding in the active site of the enzyme, CMX410 makes a covalent adduct with catalytic Serine residue, followed by rapid elimination of the sulfonate form of the inhibitor. As a result of the reaction between CMX410 and Serine hydroxyl, the backbone of the enzyme forms a β-lactam structure, permanently disabling it. The mechanism was elucidated by crystallography, capturing all states of the reaction in crystal structure.
