Literature summary for 4.1.1.17 extracted from

Wu, D.; 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 (2015), Sci. Rep., 5, 14738 .

Cloned(Commentary)

Cloned (Comment)	Organism
gene ODC1, recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21(DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme in complex with N-terminally truncated Antizyme1 (AZ1), hanging-drop vapor diffusion method, mixing of 0.001 ml of 7.7 mg/ml ODC-cAZ1 protein complex in 20 mM Tris, pH 8.5, 150 mM NaCl, and 2 mM DTT, with 0.001 ml of reservoir solution containing 0.2 M di-ammonium tartrate and 20% PEG 3350, 15°C, X-ray diffraction structure determination and analysis at 3.20 A resolution	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant enzyme in complex with N-terminally truncated Antizyme1 (AZ1), hanging-drop vapor diffusion method, mixing of 0.001 ml of 7.7 mg/ml ODC-cAZ1 protein complex in 20 mM Tris, pH 8.5, 150 mM NaCl, and 2 mM DTT, with 0.001 ml of reservoir solution containing 0.2 M di-ammonium tartrate and 20% PEG 3350, 15°C, X-ray diffraction structure determination and analysis at 3.20 A resolution

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
Antizyme1	AZ1, molecular basis for the inactivation of ODC by AZ1, analysis of the interactions between ODC and AZ1, overview. The ODC-cAZ1 complex forms a heterodimer, which consists of one ODC monomer and one AZ1 molecule, AZ1 is embedded into a concave surface formed between the N- and C-domains of ODC. Binding of the truncated cAZ1 to ODC occludes the binding of a second molecule of ODC to form the active homodimer, thus the substrate binding site is disrupted and ODC is inactivated. 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. AZ1 inhibits ODC activity, exhibits anti-tumor activities, and may be considered a tumor suppressor	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-ornithine	Homo sapiens	-	putrescine + CO2	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P11926	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant GST-tagged enzyme from Escherichia coli strain BL21(DE3) by two times glutathione affinity chromatography and gel filtration	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-ornithine	-	Homo sapiens	putrescine + CO2	-	?

Subunits

Subunits	Comment	Organism
homodimer	active enzyme form	Homo sapiens
More	the interface of the ODC homodimer contains two active sites for the ornithine decarboxylation reaction. Each active site is composed of one pyridoxal 5'-phosphate binding site, made up mainly of the N-terminal domain of one monomer, and one substrate binding site, made up mainly of the C-terminal domain of the second monomer	Homo sapiens

Synonyms

Synonyms	Comment	Organism
ODC	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
pyridoxal 5'-phosphate	each active site of the homodimer is composed of one pyridoxal 5'-phosphate binding site, made up mainly of the N-terminal domain of one monomer	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	disruption of enzyme ODC function by inhibitors renders cells non-viable and causes embryonic lethality	Homo sapiens
metabolism	ornithine decarboxylase (ODC) catalyzes the first and rate-limiting step of polyamine biosynthesis in humans	Homo sapiens
additional information	structural basis of ornithine decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1	Homo sapiens
physiological function	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. ODC is indispensable because of its central role in polyamine biosynthesis, because the polyamine products play essential roles in normal cell growth and differentiation. The enzyme is degraded by the 26S proteasome. Ornithine decarboxylase inactivation by AZ1 leads to accelerated degradation	Homo sapiens