biostudies-literatureLynch EMHHS | NIH | NIH Office of the DirectorHHS | NIH | National Institute of General Medical SciencesNIAID NIH HHSHHS | NIH | National Institute of Allergy and Infectious DiseasesNIGMS NIH HHSNIH HHSe2107968118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8501788biostudies-literatureUnknown118(40)Cytidine triphosphate synthase 1 (CTPS1) is necessary for an effective immune response, as revealed by severe immunodeficiency in CTPS1-deficient individuals [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]). CTPS1 expression is up-regulated in activated lymphocytes to expand CTP pools [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]), satisfying increased demand for nucleic acid and lipid synthesis [L. D. Fairbanks, M. Bofill, K. Ruckemann, H. A. Simmonds], [<i>J. Biol. Chem.</i> ] [270], [29682-29689] ([1995]). Demand for CTP in other tissues is met by the CTPS2 isoform and nucleoside salvage pathways [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]). Selective inhibition of the proliferative CTPS1 isoform is therefore desirable in thProceedings of the National Academy of Sciences of the United States of AmericaStructural basis for isoform-specific inhibition of human CTPS1.PMC8501788GM007270R01 AI153048S10 OD023476GM118396R01 GM118396S10OD032290AI153048T32 GM007270Lynch EMHansen JMQuispe JDKaila NAlbanese SMcElwee JJKennedy MAKreutter KDKollman JMVerras ABorrelli KDiMattia MAToms AVvan Zundert GCPfalseStructural basis for isoform-specific inhibition of human CTPS1.Cytidine triphosphate synthase 1 (CTPS1) is necessary for an effective immune response, as revealed by severe immunodeficiency in CTPS1-deficient individuals [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]). CTPS1 expression is up-regulated in activated lymphocytes to expand CTP pools [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]), satisfying increased demand for nucleic acid and lipid synthesis [L. D. Fairbanks, M. Bofill, K. Ruckemann, H. A. Simmonds], [<i>J. Biol. Chem.</i> ] [270], [29682-29689] ([1995]). Demand for CTP in other tissues is met by the CTPS2 isoform and nucleoside salvage pathways [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]). Selective inhibition of the proliferative CTPS1 isoform is therefore desirable in th2021-01-01T00:00:00Z2021 Oct2026-06-12T08:59:44.492Z2025-02-19T00:03:22.107ZS-EPMC85017883458399410.1073/pnas.2107968118