Dataset Information


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.


PROVIDER: S-EPMC2327289 | BioStudies | 2008-01-01

REPOSITORIES: biostudies

Similar Datasets

2009-01-01 | S-EPMC2785365 | BioStudies
2011-01-01 | S-EPMC3170320 | BioStudies
2005-01-01 | S-EPMC1134669 | BioStudies
2011-01-01 | S-EPMC3084279 | BioStudies
2000-01-01 | S-EPMC1220902 | BioStudies
2013-01-01 | S-EPMC3543441 | BioStudies
1000-01-01 | S-EPMC535087 | BioStudies
2014-01-01 | S-EPMC4139326 | BioStudies
2014-01-01 | S-EPMC4066113 | BioStudies
1998-01-01 | S-EPMC1219064 | BioStudies