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Open data
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Basic information
| Entry | Database: PDB / ID: 9vmm | |||||||||||||||||||||||||||
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| Title | human CTPS1 with 2CTP and DON | |||||||||||||||||||||||||||
Components | CTP synthase 1 | |||||||||||||||||||||||||||
Keywords | STRUCTURAL PROTEIN / CTP synthase / CTP / DON / cytosolic protein | |||||||||||||||||||||||||||
| Function / homology | Function and homology informationcytoophidium / CTP synthase (glutamine hydrolysing) / CTP synthase activity / 'de novo' CTP biosynthetic process / pyrimidine nucleobase biosynthetic process / Interconversion of nucleotide di- and triphosphates / CTP biosynthetic process / nucleobase-containing compound metabolic process / B cell proliferation / T cell proliferation ...cytoophidium / CTP synthase (glutamine hydrolysing) / CTP synthase activity / 'de novo' CTP biosynthetic process / pyrimidine nucleobase biosynthetic process / Interconversion of nucleotide di- and triphosphates / CTP biosynthetic process / nucleobase-containing compound metabolic process / B cell proliferation / T cell proliferation / response to xenobiotic stimulus / ATP binding / identical protein binding / membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||||||||
Authors | Guo, C.J. / Bao, X.J. / Liu, J.L. | |||||||||||||||||||||||||||
| Funding support | China, 1items
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Citation | Journal: Cell Biosci / Year: 2025Title: Filamentation of hCTPS1 with CTP. Authors: Chen-Jun Guo / Xiaojie Bao / Ji-Long Liu / ![]() Abstract: 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 ...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. | |||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9vmm.cif.gz | 429.3 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9vmm.ent.gz | 350.8 KB | Display | PDB format |
| PDBx/mmJSON format | 9vmm.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9vmm_validation.pdf.gz | 1.9 MB | Display | wwPDB validaton report |
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| Full document | 9vmm_full_validation.pdf.gz | 1.9 MB | Display | |
| Data in XML | 9vmm_validation.xml.gz | 65.9 KB | Display | |
| Data in CIF | 9vmm_validation.cif.gz | 101.4 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vm/9vmm ftp://data.pdbj.org/pub/pdb/validation_reports/vm/9vmm | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 65191MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
| #1: Protein | Mass: 66777.297 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CTPS1, CTPS / Production host: ![]() References: UniProt: P17812, CTP synthase (glutamine hydrolysing) #2: Chemical | ChemComp-CTP / #3: Chemical | ChemComp-MG / Has ligand of interest | Y | Has protein modification | N | |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: hCTPS1 with 2CTP and DON / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 8 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm |
| Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
| 3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 989280 / Symmetry type: POINT |
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About Yorodumi




Homo sapiens (human)
China, 1items
Citation

PDBj








FIELD EMISSION GUN