Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase-like Antizyme Inhibitor
Antizyme inhibitor (AZI) is homologous to the fold type III PLP-dependent enzyme ODC but does not retain any decarboxylase activity. Like ODC, AZI is presumed to exist as a homodimer. Antizyme is a regulatory protein that binds directly to the ODC monomer to block its active site, leading to its degradation by the 26S proteasome. AZI binds to Antizyme with a higher affinity than ODC, preventing the formation of the Antizyme-ODC complex. Thus, AZI blocks the ability of Antizyme to promote ODC degradation, which leads to increased ODC enzymatic activity and polyamine levels. AZI also prevents the degradation of other proteins regulated by Antizyme, such as cyclin D1.
Comment:The antizyme inhibitor (AzI) crystallizes as a dimer, whose interface displays a smaller buried surface area compared to the ornithine decarboxylase dimer interface. The AzI dimer may not be physiological. Biochemical studies suggest that AzI exists as a monomer in solution.
Structure:3BTN; Interface between subunits in Mus musculus Antizyme Inhibitor homodimer; defined at 3.5A contacts. - View structure with Cn3D