5BWA

Crystal structure of ODC-PLP-AZ1 ternary complex

Summary for 5BWA

• Entry DOI: 10.2210/pdb5bwa/pdb
• Descriptor: Ornithine decarboxylase, Ornithine decarboxylase antizyme 1, PYRIDOXAL-5'-PHOSPHATE (3 entities in total)
• Functional Keywords: ornithine decarboxylase, antizyme1, ornithine decarboxylase-antizyme1 complex, polyamine biosynthesis, polyamine homeostasis, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 69547.40

Authors

Wu, D.H. (deposition date: 2015-06-07, release date: 2015-12-09, Last modification date: 2023-11-08)

Primary citation

Wu, D.H.,Kaan, H.Y.,Zheng, X.,Tang, X.,He, Y.,Vanessa Tan, Q.,Zhang, N.,Song, H.
Structural basis of Ornithine Decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1
Sci Rep, 5:14738-14738, 2015

PubMed Abstract: Ornithine decarboxylase (ODC) catalyzes the first and rate-limiting step of polyamine biosynthesis in humans. Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis. Excessive accumulation of polyamines has a cytotoxic effect on cells and elevated level of ODC activity is associated with cancer development. To maintain normal cellular proliferation, regulation of polyamine synthesis is imposed by Antizyme1 (AZ1). The expression of AZ1 is induced by a ribosomal frameshifting mechanism in response to increased intracellular polyamines. AZ1 regulates polyamine homeostasis by inactivating ODC activity and enhancing its degradation. Here, we report the structure of human ODC in complex with N-terminally truncated AZ1 (cAZ1). The structure shows cAZ1 binding to ODC, which occludes the binding of a second molecule of ODC to form the active homodimer. Consequently, the substrate binding site is disrupted and ODC is inactivated. Structural comparison shows that the binding of cAZ1 to ODC causes a global conformational change of ODC and renders its C-terminal region flexible, therefore exposing this region for degradation by the 26S proteasome. Our structure provides the molecular basis for the inactivation of ODC by AZ1 and sheds light on how AZ1 promotes its degradation.

PubMed: 26443277
DOI: 10.1038/srep14738

Experimental method

X-RAY DIFFRACTION (3.2 Å)