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CTP synthase 1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 3215

Nomenclature: CTP synthase 1

Family: Nucleotide turnover

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 591 1p34.2 CTPS1 CTP synthase 1
Mouse - 591 4 56.52 cM Ctps1 cytidine 5'-triphosphate synthase 1
Rat - 591 5q36 Ctps1 CTP synthase 1
Previous and Unofficial Names Click here for help
cytidine 5'-triphosphate synthase | Ctps | cytidine 5'-triphosphate synthase | cytidine 5'-triphosphate synthetase | uridine triphosphate aminase
Database Links Click here for help
Alphafold P17812 (Hs), Q922Y4 (Mm)
BRENDA 6.3.4.2
Ensembl Gene ENSG00000171793 (Hs), ENSMUSG00000028633 (Mm), ENSRNOG00000009963 (Rn)
Entrez Gene 1503 (Hs), 51797 (Mm), 313560 (Rn)
Human Protein Atlas ENSG00000171793 (Hs)
KEGG Enzyme 6.3.4.2
KEGG Gene hsa:1503 (Hs), mmu:51797 (Mm), rno:313560 (Rn)
OMIM 123860 (Hs)
Pharos P17812 (Hs)
UniProtKB P17812 (Hs), Q922Y4 (Mm)
Wikipedia CTPS1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Human CTPS1 bound to inhibitor T35
PDB Id:  7MIG
Ligand:  compound 27 [PMID: 36449304]
Resolution:  2.9Å
Species:  Human
References:  1
Enzyme Reaction Click here for help
EC Number: 6.3.4.2

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 27 [PMID: 36449304] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Inhibition 7.6 pIC50 4
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [4]
compound 27 [PMID: 36449304] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Inhibition 7.6 pIC50 4
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [4]
compound 27 [PMID: 36449304] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 4
⤷ pIC50 7.5 (IC50 3.2x10-8 M) [4]
View species-specific inhibitor tables
Immunopharmacology Comments
CTPS1 is critical for the proliferation of lymphoid cells [3]. Reduced expression/function of CTPS1 causes an immunodeficiency that is characterised by the failure of T and B cell proliferation in response to infection [2]. It is hypothesised that selective targeting of CTPS1 by pharmacological inhibitors may provide a mechanism to reduce aberrant immune cell proliferation in inflammatory/autoimmune conditions and haematological malignancies.

References

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1. Lynch EM, DiMattia MA, Albanese S, van Zundert GCP, Hansen JM, Quispe JD, Kennedy MA, Verras A, Borrelli K, Toms AV et al.. (2021) Structural basis for isoform-specific inhibition of human CTPS1. Proc Natl Acad Sci U S A, 118 (40): e2107968118. [PMID:34583994]

2. Martin E, Minet N, Boschat AC, Sanquer S, Sobrino S, Lenoir C, de Villartay JP, Leite-de-Moraes M, Picard C, Soudais C et al.. (2020) Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation. JCI Insight, 5 (5): e133880. [PMID:32161190]

3. Martin E, Palmic N, Sanquer S, Lenoir C, Hauck F, Mongellaz C, Fabrega S, Nitschké P, Esposti MD, Schwartzentruber J et al.. (2014) CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature, 510 (7504): 288-92. [PMID:24870241]

4. Novak A, Laughton D, Lane R, Blackham E, Thomas J, Chatzopoulou E, Wrigglesworth J, Quddus A, Ahmed S, Cousin D et al.. (2022) Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation. J Med Chem, 65 (24): 16640-16650. [PMID:36449304]

How to cite this page

Nucleotide turnover: CTP synthase 1. Last modified on 23/08/2023. Accessed on 09/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3215.