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| | ==STRUCTURE of HUMAN ORNITHINE DECARBOXYLASE IN COMPLEX WITH A C-TERMINAL FRAGMENT OF ANTIZYME== | | ==STRUCTURE of HUMAN ORNITHINE DECARBOXYLASE IN COMPLEX WITH A C-TERMINAL FRAGMENT OF ANTIZYME== |
| - | <StructureSection load='4zgy' size='340' side='right' caption='[[4zgy]], [[Resolution|resolution]] 2.63Å' scene=''> | + | <StructureSection load='4zgy' size='340' side='right'caption='[[4zgy]], [[Resolution|resolution]] 2.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zgy]] 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=4ZGY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZGY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zgy]] 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=4ZGY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZGY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.63Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1d7k|1d7k]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <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=4zgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zgy OCA], [https://pdbe.org/4zgy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zgy RCSB], [https://www.ebi.ac.uk/pdbsum/4zgy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zgy 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=4zgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zgy OCA], [http://pdbe.org/4zgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zgy RCSB], [http://www.ebi.ac.uk/pdbsum/4zgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zgy 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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| | </div> | | </div> |
| | <div class="pdbe-citations 4zgy" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4zgy" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antizyme inhibitor 3D structures|Antizyme inhibitor 3D structures]] |
| | + | *[[Ornithine decarboxylase|Ornithine decarboxylase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ornithine decarboxylase]] | + | [[Category: Large Structures]] |
| - | [[Category: Chan, N L]] | + | [[Category: Chan NL]] |
| - | [[Category: Wu, H Y]] | + | [[Category: Wu HY]] |
| - | [[Category: Antizyme]]
| + | |
| - | [[Category: Beta-sheet domain]]
| + | |
| - | [[Category: Decarboxylation]]
| + | |
| - | [[Category: Lyase-lyase inhibitor complex]]
| + | |
| - | [[Category: Plasma]]
| + | |
| - | [[Category: Tim-barrel domain]]
| + | |
| Structural highlights
Function
DCOR_HUMAN
Publication Abstract from PubMed
Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins antizyme isoform 1 (Az1) and antizyme inhibitor (AzIN). Az1 suppresses polyamine production by inhibiting the assembly of the functional ODC homodimer and, most uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by competing with ODC for Az1 binding. The structural basis of the Az1-mediated regulation of polyamine homeostasis has remained elusive. Here we report crystal structures of human Az1 complexed with either ODC or AzIN. Structural analysis revealed that Az1 sterically blocks ODC homodimerization. Moreover, Az1 binding triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC, which illustrates how a substrate protein may be primed upon association with Az1 for ubiquitin-independent proteasome recognition. Dynamic and functional analyses further indicated that the Az1-induced binding and degradation of ODC by proteasome can be decoupled, with the intrinsically disordered C-terminal tail fragment of ODC being required only for degradation but not binding. Finally, the AzIN-Az1 structure suggests how AzIN may effectively compete with ODC for Az1 to restore polyamine production. Taken together, our findings offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation.
Structural basis of antizyme-mediated regulation of polyamine homeostasis.,Wu HY, Chen SF, Hsieh JY, Chou F, Wang YH, Lin WT, Lee PY, Yu YJ, Lin LY, Lin TS, Lin CL, Liu GY, Tzeng SR, Hung HC, Chan NL Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11229-34. doi:, 10.1073/pnas.1508187112. Epub 2015 Aug 24. PMID:26305948[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu HY, Chen SF, Hsieh JY, Chou F, Wang YH, Lin WT, Lee PY, Yu YJ, Lin LY, Lin TS, Lin CL, Liu GY, Tzeng SR, Hung HC, Chan NL. Structural basis of antizyme-mediated regulation of polyamine homeostasis. Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11229-34. doi:, 10.1073/pnas.1508187112. Epub 2015 Aug 24. PMID:26305948 doi:http://dx.doi.org/10.1073/pnas.1508187112
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