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| ==cryoEM structure of the product-bound human CTP synthase 2 filament== | | ==cryoEM structure of the product-bound human CTP synthase 2 filament== |
- | <StructureSection load='6pk7' size='340' side='right'caption='[[6pk7]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <SX load='6pk7' size='340' side='right' viewer='molstar' caption='[[6pk7]], [[Resolution|resolution]] 3.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6pk7]] is a 4 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=6PK7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PK7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pk7]] is a 4 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=6PK7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PK7 FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTPS2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene></td></tr> |
- | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/CTP_synthase_(glutamine_hydrolyzing) CTP synthase (glutamine hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.2 6.3.4.2] </span></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=6pk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pk7 OCA], [https://pdbe.org/6pk7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pk7 RCSB], [https://www.ebi.ac.uk/pdbsum/6pk7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pk7 ProSAT]</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=6pk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pk7 OCA], [http://pdbe.org/6pk7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pk7 RCSB], [http://www.ebi.ac.uk/pdbsum/6pk7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pk7 ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/PYRG2_HUMAN PYRG2_HUMAN]] Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides.<ref>PMID:10899599</ref> <ref>PMID:16179339</ref> | + | [https://www.uniprot.org/uniprot/PYRG2_HUMAN PYRG2_HUMAN] Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides.<ref>PMID:10899599</ref> <ref>PMID:16179339</ref> |
- | <div style="background-color:#fffaf0;">
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- | == Publication Abstract from PubMed ==
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- | Many enzymes assemble into defined oligomers, providing a mechanism for cooperatively regulating activity. Recent studies have described a mode of regulation in which enzyme activity is modulated by polymerization into large-scale filaments. Here we describe an ultrasensitive form of polymerization-based regulation employed by human CTP synthase 2 (CTPS2). Cryo-EM structures reveal that CTPS2 filaments dynamically switch between active and inactive forms in response to changes in substrate and product levels. Linking the conformational state of many CTPS2 subunits in a filament results in highly cooperative regulation, greatly exceeding the limits of cooperativity for the CTPS2 tetramer alone. The structures reveal a link between conformation and control of ammonia channeling between the enzyme's active sites, and explain differences in regulation of human CTPS isoforms. This filament-based mechanism of enhanced cooperativity demonstrates how the widespread phenomenon of enzyme polymerization can be adapted to achieve different regulatory outcomes.
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- | Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments.,Lynch EM, Kollman JM Nat Struct Mol Biol. 2019 Dec 23. pii: 10.1038/s41594-019-0352-5. doi:, 10.1038/s41594-019-0352-5. PMID:31873303<ref>PMID:31873303</ref>
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- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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- | </div>
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- | <div class="pdbe-citations 6pk7" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
- | </StructureSection> | + | </SX> |
- | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Kollman, J M]] | + | [[Category: Kollman JM]] |
- | [[Category: Lynch, E M]] | + | [[Category: Lynch EM]] |
- | [[Category: Enzyme]]
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- | [[Category: Filament]]
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- | [[Category: Protein fibril]]
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