Ornithine decarboxylase (ODC) is a pyridoxal 5’-phosphate (PLP)-dependent enzyme which catalyses the first and rate-limiting step in the biosynthesis of polyamines. Polyamines are critical for cell proliferation and are involved in many cellular processes including DNA division, replication and apoptosis. It is also a critical enzyme for many eukaryotic parasites including Trypanosoma brucei, which causes human African sleeping sickness. G418 sulfate (G418/ Geneticin) is an weak inhibitor of ODC that is non-competitive with substrate. It consistently inhibits ODC and could provide an alternative to the highly toxic drugs used to treat African sleeping sickness. This model shows T. brucei ODC bound to both G418 and its substrate analogue D-Ornithine. The Annotations show the G418 binding site and interactions with ODC as well as several conformational changes triggered by this binding. By Charmaine Cheung and Catherine Chen.
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