Ornithine decarboxylase inhibition by G418

**Ornithine decarboxylase** is an enzyme involved in polyamine synthesis that is critical to *Trypanosoma brucei*, the cause of african sleeping sickness. Polyamines are polycationic compounds that are vital in the synthesis of biological molecules such as DNA, RNA and proteins. ODC converts L-Ornithine into the polyamine Putrescine. This model is an ODC dimer in complex with G418 and D-Ornithine. G418 is a non-competitive inhibitor of ODC. Some of the annotations demonstrate how G418 allosterically inhibits ODC. Included here are the disordering of the active site loop and the rotation of several vital residues out of the active site. Many of these mechanisms are novel, offering new insights of potential drug design that could overcome the poor pharmacology of approved drugs such as DFMO.