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| | <StructureSection load='5bwa' size='340' side='right'caption='[[5bwa]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='5bwa' size='340' side='right'caption='[[5bwa]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5bwa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BWA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5bwa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ODC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), OAZ1, OAZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5bwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwa OCA], [https://pdbe.org/5bwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bwa RCSB], [https://www.ebi.ac.uk/pdbsum/5bwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwa ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ornithine_decarboxylase Ornithine decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.17 4.1.1.17] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5bwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwa OCA], [http://pdbe.org/5bwa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bwa RCSB], [http://www.ebi.ac.uk/pdbsum/5bwa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwa ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OAZ1_HUMAN OAZ1_HUMAN]] Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake by binding to and targeting ODC1 for degradation (PubMed:17900240). Stabilizes AZIN2 by interfering with its ubiquitination. Also inhibits cellular uptake of polyamines by inactivating the polyamine uptake transporter. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. Involved in the translocation of AZNI2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol.<ref>PMID:12097147</ref> <ref>PMID:17900240</ref> | + | [https://www.uniprot.org/uniprot/DCOR_HUMAN DCOR_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ornithine decarboxylase]]
| + | [[Category: Wu DH]] |
| - | [[Category: Wu, D H]] | + | |
| - | [[Category: Antizyme1]]
| + | |
| - | [[Category: Lyase-lyase inhibitor complex]]
| + | |
| - | [[Category: Ornithine decarboxylase-antizyme1 complex]]
| + | |
| - | [[Category: Polyamine biosynthesis]]
| + | |
| - | [[Category: Polyamine homeostasis]]
| + | |
| Structural highlights
Function
DCOR_HUMAN
Publication Abstract from PubMed
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.
Structural basis of Ornithine Decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1.,Wu D, Kaan HY, Zheng X, Tang X, He Y, Vanessa Tan Q, Zhang N, Song H Sci Rep. 2015 Oct 7;5:14738. doi: 10.1038/srep14738. PMID:26443277[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu D, Kaan HY, 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. 2015 Oct 7;5:14738. doi: 10.1038/srep14738. PMID:26443277 doi:http://dx.doi.org/10.1038/srep14738
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