Ornithine decarboxylase (OCD) is a homodimer which catalyses the first step in the conversion of L-ornithine to the polyamine putrescine, an essential molecule in many cellular processes. This requires a cofactor, pyridoxal 5′-phosphate (PLP), to interact with ornithine. This model demonstrates the interactions which occur with the suicide inhibitor α-difluoromethylornithine (DFMO), including those which form the active site at the aromatic-heavy interface of the dimers, position and stabilise the molecule, and irreversibly bond with it by forming covalent bonds, both with PLP and OCD. DFMO is a WHO “essential” medicine, forming a common treatment for infection with Trypanasoma brucei, the causative agent of African Sleeping Sickness, although some mutants exhibit resistance to the drug. One such mutant OCD, K69A, is shown here, along with the mechanism by which it evades inhibition.
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