View source for 9vmm


==human CTPS1 with 2CTP and DON==
<StructureSection load='9vmm' size='340' side='right'caption='[[9vmm]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vmm]] 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=9VMM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VMM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=9vmm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vmm OCA], [https://pdbe.org/9vmm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vmm RCSB], [https://www.ebi.ac.uk/pdbsum/9vmm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vmm ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PYRG1_HUMAN PYRG1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. A unique and recessive G to C mutation probably affecting a splice donor site at the junction of intron 17-18 and exon 18 has been identified in all patients. It results in expression of an abnormal transcript lacking exon 18 and a complete loss of the expression of the protein.<ref>PMID:24870241</ref> 
== Function ==
[https://www.uniprot.org/uniprot/PYRG1_HUMAN PYRG1_HUMAN] This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity.<ref>PMID:16179339</ref> <ref>PMID:24870241</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
CTP synthase (CTPS) is a key enzyme in de novo CTP synthesis, playing a critical role in nucleotide metabolism and cellular proliferation. Human CTPS1 (hCTPS1), one of the two CTPS isoforms, is essential for immune responses and is highly expressed in proliferating cells, making it a promising therapeutic target for immune-related diseases and cancer. Despite its importance, the regulatory mechanisms governing hCTPS1 activity remain poorly understood. Here, we reveal that CTP, the product of CTPS, acts as a key regulator for hCTPS1 filamentation. Using cryo-electron microscopy (cryo-EM), we resolve the high-resolution structure of CTP-bound hCTPS1 filaments, uncovering the molecular details of CTP binding and its role in filament assembly. Importantly, we demonstrate that CTP generated from the enzymatic reaction does not trigger filament disassembly, suggesting a conserved regulatory pattern. Furthermore, by analyzing the binding modes of two distinct CTP-binding pockets, we provide evidence that this filamentation mechanism is evolutionarily conserved across species, particularly in eukaryotic CTPS. Our findings not only elucidate a novel regulatory mechanism of hCTPS1 activity but also deepen the understanding of how metabolic enzymes utilize filamentation as a conserved strategy for functional regulation. This study opens new avenues for targeting hCTPS1 in therapeutic interventions.

Filamentation of hCTPS1 with CTP.,Guo CJ, Bao X, Liu JL Cell Biosci. 2025 Jul 30;15(1):112. doi: 10.1186/s13578-025-01450-6. PMID:40739251<ref>PMID:40739251</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9vmm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bao XJ]]
[[Category: Guo CJ]]
[[Category: Liu JL]]