title: Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function.
abstract: Antizyme inhibitor (AzI) regulates cellular polyamine homeostasis by binding to the polyamine-induced protein, Antizyme (Az), with greater affinity than ornithine decarboxylase (ODC). AzI is highly homologous to 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 2.05 A resolution. Both AzI and ODC crystallize as a dimer. However, fewer interactions at the dimer interface, 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 nonphysiological. In addition, the absence of residues and interactions required for pyridoxal 5'-phosphate (PLP) binding suggests 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 is unable to bind PLP provide two independent explanations for its lack of enzymatic activity and suggest the basis for its enhanced affinity toward Az.
authors: The Israel Structural Proteomics Center, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Shira
authors: S
authors: Albeck
authors: Orly
authors: O
authors: Dym
authors: Tamar
authors: T
authors: Unger
authors: Zohar
authors: Z
authors: Snapir
authors: Zippy
authors: Z
authors: Bercovich
authors: Chaim
authors: C
authors: Kahana
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009955:Ornithine Decarboxylase / Q000737:chemistry*; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D002352:Carrier Proteins; C039317:ornithine decarboxylase antizyme inhibitor; D009955:Ornithine Decarboxylase