Antizyme inhibitor (AzI) regulates cellular polyamine homeostasis by binding to the polyamine-induced protein, Antizyme (Az), with greater affinity than ODC. AzI is highly homologous to ornithine decarboxylase (ODC), but is not enzymatically active . In order to understand these specific characteristics of AzI and its differences from ODC, we determined the 3D structure of mouse AzI to 2.05Å resolution. Both AzI and ODC crystallize as a
(one monomer in red and the other in green).
However, fewer interactions at the dimer
, a smaller buried surface area, and lack of symmetry of the interactions between residues from the two monomers in the AzI structure suggest that this dimeric structure is non-physiological. In addition, the absence of residues and interactions required for
binding suggest that AzI does not bind PLP. Biochemical studies confirmed the lack of PLP binding and revealed that AzI exists as a monomer in solution while ODC is dimeric. Our findings that AzI exists as a monomer and its inability to bind PLP provide two independent explanations for its lack of enzymatic activity, and suggest the basis for its enhanced affinity towards Az.