Ornithine decarboxylase (Trypanosoma brucei) (ODC)

Ornithine decarboxylase in Trypanosoma brucei is a homodimeric, pyridoxal 5'-phosphate-dependent enzyme that catalyzes the conversion of ornithine to putrescine—the initial, rate-limiting step in polyamine biosynthesis. This pathway is vital for parasite cell division and survival, making ODC an attractive drug target for African sleeping sickness. The enzyme is characterized by unique structural features, including a β/α-barrel N-terminal domain and a Greek key β-barrel C-terminal domain, and forms a tight dimeric interface. ODC's activity is essential for maintaining trypanothione, which protects the parasite from oxidative stress. Alpha-difluoromethylornithine (DFMO), a suicide inhibitor of ODC, is clinically approved and effective against T. brucei gambiense and is recommended together with nifurtimox for late-stage infection. The enzyme differs from its mammalian counterpart in regulatory mechanisms and turnover, supporting the development of selective parasite-specific inhibitors.

Other names

ODCOrnithine decarboxylaseTrypanosoma brucei ODCTbODCTrypanosoma brucei gambiense ornithine decarboxylase

Irreversible inhibition of ODC enzymatic activity, leading to depletion of polyamine and trypanothione pools, arresting cell growth, and causing rapid parasite death; DFMO acts as a suicide inhibitor, forming a covalent bond in the active site