Structural basis of antizyme-mediated regulation of polyamine homeostasis
Abstract
Polyamines are small organic compounds that carry multiple positive charges at physiological pH. With a high capacity to interact with the acidic surface patches of proteins and nucleic acids, polyamines may regulate a variety of cellular processes, and the fluctuations in the intracellular polyamine levels are rigorously controlled during cell growth and differentiation through the interplay between the enzyme ornithine decarboxylase (ODC) and two regulatory proteins: antizyme (Az) and antizyme inhibitor (AzIN). ODC initiates the polyamine biosynthetic pathway, whereas Az decreases polyamine concentrations by both inhibiting ODC activity and channeling ODC for proteolytic degradation. AzIN neutralizes Az function to restore polyamine levels. Here we provide the long-sought structural information and previously unidentified functional insights into this delicate regulatory circuit.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- September 2015
- DOI:
- 10.1073/pnas.1508187112
- Bibcode:
- 2015PNAS..11211229W