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| | <StructureSection load='5g1p' size='340' side='right'caption='[[5g1p]], [[Resolution|resolution]] 3.19Å' scene=''> | | <StructureSection load='5g1p' size='340' side='right'caption='[[5g1p]], [[Resolution|resolution]] 3.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5g1p]] is a 6 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=5G1P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5G1P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5g1p]] is a 6 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=5G1P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G1P FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CP:PHOSPHORIC+ACID+MONO(FORMAMIDE)ESTER'>CP</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]] 3.19Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5g1n|5g1n]], [[5g1o|5g1o]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CP:PHOSPHORIC+ACID+MONO(FORMAMIDE)ESTER'>CP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase Aspartate carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.2 2.1.3.2] </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=5g1p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g1p OCA], [https://pdbe.org/5g1p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g1p RCSB], [https://www.ebi.ac.uk/pdbsum/5g1p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g1p ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5g1p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g1p OCA], [http://pdbe.org/5g1p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g1p RCSB], [http://www.ebi.ac.uk/pdbsum/5g1p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g1p ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PYR1_HUMAN PYR1_HUMAN]] This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). | + | [https://www.uniprot.org/uniprot/PYR1_HUMAN PYR1_HUMAN] This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). |
| | <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 5g1p" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5g1p" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[CAD protein 3D structures|CAD protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aspartate carbamoyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Grande-Garcia, A]] | + | [[Category: Grande-Garcia A]] |
| - | [[Category: Moreno-Morcillo, M D]] | + | [[Category: Moreno-Morcillo MD]] |
| - | [[Category: Ramon-Maiques, S]] | + | [[Category: Ramon-Maiques S]] |
| - | [[Category: Ruiz-Ramos, A]] | + | [[Category: Ruiz-Ramos A]] |
| - | [[Category: Cad]]
| + | |
| - | [[Category: Carbamoyl phosphate synthetase]]
| + | |
| - | [[Category: Cooperativity]]
| + | |
| - | [[Category: De novo pyrimidine synthesis]]
| + | |
| - | [[Category: Dihydroorotase]]
| + | |
| - | [[Category: Transcarbamoylase]]
| + | |
| - | [[Category: Transcarbamylase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PYR1_HUMAN This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
Publication Abstract from PubMed
CAD, the multienzymatic protein that initiates and controls de novo synthesis of pyrimidines in animals, associates through its aspartate transcarbamoylase (ATCase) domain into particles of 1.5 MDa. Despite numerous structures of prokaryotic ATCases, we lack structural information on the ATCase domain of CAD. Here, we report the structure and functional characterization of human ATCase, confirming the overall similarity with bacterial homologs. Unexpectedly, human ATCase exhibits cooperativity effects that reduce the affinity for the anti-tumoral drug PALA. Combining structural, mutagenic, and biochemical analysis, we identified key elements for the necessary regulation and transmission of conformational changes leading to cooperativity between subunits. Mutation of one of these elements, R2024, was recently found to cause the first non-lethal CAD deficit. We reproduced this mutation in human ATCase and measured its effect, demonstrating that this arginine is part of a molecular switch that regulates the equilibrium between low- and high-affinity states for the ligands.
Structure and Functional Characterization of Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral Drug PALA.,Ruiz-Ramos A, Velazquez-Campoy A, Grande-Garcia A, Moreno-Morcillo M, Ramon-Maiques S Structure. 2016 May 31. pii: S0969-2126(16)30079-X. doi:, 10.1016/j.str.2016.05.001. PMID:27265852[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ruiz-Ramos A, Velazquez-Campoy A, Grande-Garcia A, Moreno-Morcillo M, Ramon-Maiques S. Structure and Functional Characterization of Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral Drug PALA. Structure. 2016 May 31. pii: S0969-2126(16)30079-X. doi:, 10.1016/j.str.2016.05.001. PMID:27265852 doi:http://dx.doi.org/10.1016/j.str.2016.05.001
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