Antizyme Inhibitor: Difference between revisions
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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 | 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 | ||
<scene name='3btn/Azi/1'>dimer</scene> (one monomer in | <scene name='3btn/Azi/1'>dimer</scene> (one monomer in blue and the other in green). | ||
However, fewer interactions at the dimer | However, fewer interactions at the dimer | ||
<scene name='3btn/Interface/2'>interface</scene>, 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 | <scene name='3btn/Interface/2'>interface</scene>, 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 | ||
<scene name='3btn/Plp/1'>PLP</scene> | <scene name='3btn/Plp/1'>PLP</scene> | ||
binding suggest that AzI does not bind PLP. A comparison to the <scene name='3btn/Plp/1'>PLP binding site of ODC</scene> revealed that AzI lacks the residues participating in PLP binding. 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. | binding suggest that AzI does not bind PLP. A comparison to the <scene name='3btn/Plp/1'>PLP binding site of ODC</scene> revealed that AzI lacks the residues participating in PLP binding. 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. | ||
