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CTP synthetase

April 16, 2024

CTP synthase is an enzyme (EC 6.3.4.2) involved in pyrimidine biosynthesis that interconverts UTP and CTP.[1][2]

CTP synthase
Identifiers
EC no.6.3.4.2
CAS no.9023-56-7
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Reaction mechanism edit

CTP (cytidine triphosphate) synthetase catalyzes the last committed step in pyrimidine nucleotide biosynthesis:[3]

ATP + UTP + glutamine → ADP + Pi + CTP + glutamate

It is the rate-limiting enzyme for the synthesis of cytosine nucleotides from both the de novo and uridine salvage pathways.[4]

The reaction proceeds by the ATP-dependent phosphorylation of UTP on the 4-oxygen atom, making the 4-carbon electrophilic and vulnerable to reaction with ammonia.[5] The source of the amino group in CTP is glutamine, which is hydrolysed in a glutamine amidotransferase domain to produce ammonia. This is then channeled through the interior of the enzyme to the synthetase domain.[6][7] Here, ammonia reacts with the intermediate 4-phosphoryl UTP.[8]

 

Isozymes edit

Two isozymes with CTP synthase activity exist in humans, encoded by the following genes:

  • CTPS – CTP synthase 1
  • CTPS2 – CTP synthase 2

Structure edit

 
Dimeric form of CTP synthase from Sulfolobus solfataricus (PDB code: 3NVA). Chain A is depicted in blue and Chain B in green.

Active CTP synthase exists as a homotetrameric enzyme. At low enzyme concentrations and in the absence of ATP and UTP, CTP synthase exists as inactive monomer. As enzyme concentration increases, it polymerizes first to a dimer (such as the form shown to the left) and, in the presence of ATP and UTP, forms a tetramer.[5][9]

The enzyme contains two major domains, responsible for the aminotransferase and synthase activity, respectively. The amidotransferase domains are located away from the tetramer interfaces and are not affected by the oligomeric state. The ATP-binding site and CTP-binding site in the synthase domain are located at the tetramer interface. It is for this reason that ATP and UTP are required for tetramerization.[10]

Regulation edit

CTP synthase is precisely regulated by the intracellular concentrations of CTP and UTP, and both hCTPS1 and hCTPS2 have been seen to be maximally active at physiological concentrations of ATP, GTP, and glutamine.[11]

The activity of human CTPS1 isozyme has been demonstrated to be inhibited by phosphorylation.[12] One major example of this is phosphorylation of the Ser-571 residue by glycogen synthase kinase 3 (GSK3) in response to low serum conditions.[13] Additionally, Ser568 has been seen to be phosphorylated by casein kinase 1, inhibiting CTP synthase activity.[11]

CTP is also subject to various forms of allosteric regulation. GTP acts as an allosteric activator that strongly promotes the hydrolysis of glutamine, but is also inhibiting to glutamine-dependent CTP formation at high concentrations.[14] This acts to balance the relative amounts of purine and pyrimidine nucleotides. The reaction product CTP also serves as an allosteric inhibitor. The triphosphate binding site overlaps with that of UTP, but the nucleoside moiety of CTP binds in an alternative pocket opposite the binding site for UTP.[15]

CTP synthase levels have been shown to be dependent on levels of the transcription factor Myc. In turn, CTP synthase activity is required for Myc related phenotypes.[16]

The glutamine analog DON has also been seen to act as an irreversible inhibitor, and has been used as an anti-cancer agent.[17]

Filaments edit

CTP synthase has been reported to form filaments in several different organisms. These include bacteria (C. crescentus),[18] yeast (S. cerevisiae),[19] fruit flies (D. melanogaster)[20] and human cells.[21] These filamentous structures have been referred to as cytoplasmic rods and rings,[22] cytoophidia (from the Greek "cyto" meaning cell and "ophidium" meaning serpent, due to the structures morphology) or simply CTP synthase filaments. It has been shown that filamentation downregulates or upregulates CTP synthase activity depending on the species.[23][24][25][26][27] In Drosophila, only one of the CTP synthase isoform forms the filament.[28] Since the discovery of this novel mode of enzyme regulation in CTP synthase, multiple other enzymes have been shown to exhibit similar characteristics, suggesting that this is an important and well conserved strategy for enzymatic regulation.[29] CTP synthase remains a model enzyme for the study of filament formation.

Clinical significance edit

Upregulated CTP synthase activity has been widely seen in human and rodent tumors.[30] Evidence from fly models[16] and human cancer cells[31] suggests that Myc-dependent cell growth may be more susceptible to suppression of CTP-synthase activity.

Mutations in the CTP synthase have been seen to confer resistance to cytotoxic drugs such as cytosine arabinoside (ara-C) in a Chinese hamster ovary (CHO) cell model of leukemia though such mutations were not found in human patients with ara-C resistance.[32]

See also edit

References edit

  1. ^ Lieberman I (October 1956). "Enzymatic amination of uridine triphosphate to cytidine triphosphate". The Journal of Biological Chemistry. 222 (2): 765–775. doi:10.1016/S0021-9258(20)89934-7. PMID 13367044.
  2. ^ Long CW, Levitzki A, Koshland DE (January 1970). "The subunit structure and subunit interactions of cytidine triphosphate synthetase". The Journal of Biological Chemistry. 245 (1): 80–87. doi:10.1016/S0021-9258(18)63424-6. PMID 5411547.
  3. ^ Koshland DE, Levitzki A (1974). "CTP Synthetase and Related Enzymes". In Boyer PD (ed.). The Enzymes (3rd ed.). New York: Academic Press. pp. 539–59. ISBN 978-0-12-122710-4.
  4. ^ van Kuilenburg AB, Meinsma R, Vreken P, Waterham HR, van Gennip AH (2000). "Isoforms of human CTP synthetase". Purine and Pyrimidine Metabolism in Man X. Advances in Experimental Medicine and Biology. Vol. 486. pp. 257–261. doi:10.1007/0-306-46843-3_50. ISBN 978-0-306-46515-4. PMID 11783495.
  5. ^ a b von der Saal W, Anderson PM, Villafranca JJ (December 1985). "Mechanistic investigations of Escherichia coli cytidine-5'-triphosphate synthetase. Detection of an intermediate by positional isotope exchange experiments". The Journal of Biological Chemistry. 260 (28): 14993–14997. doi:10.1016/S0021-9258(18)95692-9. PMID 2933396.
  6. ^ Levitzki A, Koshland DE (August 1971). "Cytidine triphosphate synthetase. Covalent intermediates and mechanisms of action". Biochemistry. 10 (18): 3365–3371. doi:10.1021/bi00794a008. PMID 4940761.
  7. ^ Endrizzi JA, Kim H, Anderson PM, Baldwin EP (June 2004). "Crystal structure of Escherichia coli cytidine triphosphate synthetase, a nucleotide-regulated glutamine amidotransferase/ATP-dependent amidoligase fusion protein and homologue of anticancer and antiparasitic drug targets". Biochemistry. 43 (21): 6447–6463. doi:10.1021/bi0496945. PMC 2891762. PMID 15157079.
  8. ^ Lewis DA, Villafranca JJ (October 1989). "Investigation of the mechanism of CTP synthetase using rapid quench and isotope partitioning methods". Biochemistry. 28 (21): 8454–8459. doi:10.1021/bi00447a027. PMID 2532543.
  9. ^ Anderson PM (June 1983). "CTP synthetase from Escherichia coli: an improved purification procedure and characterization of hysteretic and enzyme concentration effects on kinetic properties". Biochemistry. 22 (13): 3285–3292. doi:10.1021/bi00282a038. PMID 6349684.
  10. ^ Lauritsen I, Willemoës M, Jensen KF, Johansson E, Harris P (February 2011). "Structure of the dimeric form of CTP synthase from Sulfolobus solfataricus". Acta Crystallographica. Section F, Structural Biology and Crystallization Communications. 67 (Pt 2): 201–208. doi:10.1107/S1744309110052334. PMC 3034608. PMID 21301086.
  11. ^ a b Kassel KM, Higgins MJ, Hines M, Graves LM (October 2010). "Regulation of human cytidine triphosphate synthetase 2 by phosphorylation". The Journal of Biological Chemistry. 285 (44): 33727–33736. doi:10.1074/jbc.M110.178566. PMC 2962471. PMID 20739275.
  12. ^ Carman GM, Kersting MC (February 2004). "Phospholipid synthesis in yeast: regulation by phosphorylation". Biochemistry and Cell Biology. 82 (1): 62–70. doi:10.1139/o03-064. PMID 15052328.
  13. ^ Higgins MJ, Graves PR, Graves LM (October 2007). "Regulation of human cytidine triphosphate synthetase 1 by glycogen synthase kinase 3". The Journal of Biological Chemistry. 282 (40): 29493–29503. doi:10.1074/jbc.M703948200. PMID 17681942.
  14. ^ Lunn FA, MacDonnell JE, Bearne SL (January 2008). "Structural requirements for the activation of Escherichia coli CTP synthase by the allosteric effector GTP are stringent, but requirements for inhibition are lax". The Journal of Biological Chemistry. 283 (4): 2010–2020. doi:10.1074/jbc.M707803200. PMID 18003612.
  15. ^ Endrizzi JA, Kim H, Anderson PM, Baldwin EP (October 2005). "Mechanisms of product feedback regulation and drug resistance in cytidine triphosphate synthetases from the structure of a CTP-inhibited complex". Biochemistry. 44 (41): 13491–13499. doi:10.1021/bi051282o. PMC 2891682. PMID 16216072.
  16. ^ a b Aughey GN, Grice SJ, Liu JL (February 2016). "The Interplay between Myc and CTP Synthase in Drosophila". PLOS Genetics. 12 (2): e1005867. doi:10.1371/journal.pgen.1005867. PMC 4759343. PMID 26889675.
  17. ^ Ahluwalia GS, Grem JL, Hao Z, Cooney DA (1990). "Metabolism and action of amino acid analog anti-cancer agents". Pharmacology & Therapeutics. 46 (2): 243–271. doi:10.1016/0163-7258(90)90094-I. PMID 2108451.
  18. ^ Ingerson-Mahar M, Briegel A, Werner JN, Jensen GJ, Gitai Z (August 2010). "The metabolic enzyme CTP synthase forms cytoskeletal filaments". Nature Cell Biology. 12 (8): 739–746. doi:10.1038/ncb2087. PMC 3210567. PMID 20639870.
  19. ^ Noree C, Sato BK, Broyer RM, Wilhelm JE (August 2010). "Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster". The Journal of Cell Biology. 190 (4): 541–551. doi:10.1083/jcb.201003001. PMC 2928026. PMID 20713603.
  20. ^ Liu JL (May 2010). "Intracellular compartmentation of CTP synthase in Drosophila". Journal of Genetics and Genomics = Yi Chuan Xue Bao. 37 (5): 281–296. doi:10.1016/S1673-8527(09)60046-1. PMID 20513629. S2CID 206173864.
  21. ^ Chen K, Zhang J, Tastan ÖY, Deussen ZA, Siswick MY, Liu JL (September 2011). "Glutamine analogs promote cytoophidium assembly in human and Drosophila cells". Journal of Genetics and Genomics = Yi Chuan Xue Bao. 38 (9): 391–402. doi:10.1016/j.jgg.2011.08.004. PMID 21930098.
  22. ^ Carcamo WC, Satoh M, Kasahara H, Terada N, Hamazaki T, Chan JY, et al. (2011). "Induction of cytoplasmic rods and rings structures by inhibition of the CTP and GTP synthetic pathway in mammalian cells". PLOS ONE. 6 (12): e29690. Bibcode:2011PLoSO...629690C. doi:10.1371/journal.pone.0029690. PMC 3248424. PMID 22220215.
  23. ^ Lynch EM, Hicks DR, Shepherd M, Endrizzi JA, Maker A, Hansen JM, et al. (June 2017). "Human CTP synthase filament structure reveals the active enzyme conformation". Nature Structural & Molecular Biology. 24 (6): 507–514. doi:10.1038/nsmb.3407. PMC 5472220. PMID 28459447.
  24. ^ Barry RM, Bitbol AF, Lorestani A, Charles EJ, Habrian CH, Hansen JM, et al. (July 2014). "Large-scale filament formation inhibits the activity of CTP synthetase". eLife. 3: e03638. doi:10.7554/eLife.03638. PMC 4126345. PMID 25030911.
  25. ^ Aughey GN, Grice SJ, Shen QJ, Xu Y, Chang CC, Azzam G, et al. (October 2014). "Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism". Biology Open. 3 (11): 1045–1056. doi:10.1242/bio.201410165. PMC 4232762. PMID 25326513.
  26. ^ Noree C, Monfort E, Shiau AK, Wilhelm JE (August 2014). "Common regulatory control of CTP synthase enzyme activity and filament formation". Molecular Biology of the Cell. 25 (15): 2282–2290. doi:10.1091/mbc.E14-04-0912. PMC 4116302. PMID 24920825.
  27. ^ Barry RM, Gitai Z (December 2011). "Self-assembling enzymes and the origins of the cytoskeleton". Current Opinion in Microbiology. 14 (6): 704–711. doi:10.1016/j.mib.2011.09.015. PMC 3234109. PMID 22014508.
  28. ^ Azzam G, Liu JL (February 2013). "Only one isoform of Drosophila melanogaster CTP synthase forms the cytoophidium". PLOS Genetics. 9 (2): e1003256. doi:10.1371/journal.pgen.1003256. PMC 3573105. PMID 23459760.
  29. ^ Aughey GN, Liu JL (2015). "Metabolic regulation via enzyme filamentation". Critical Reviews in Biochemistry and Molecular Biology. 51 (4): 282–293. doi:10.3109/10409238.2016.1172555. PMC 4915340. PMID 27098510.
  30. ^ Kizaki H, Williams JC, Morris HP, Weber G (November 1980). "Increased cytidine 5'-triphosphate synthetase activity in rat and human tumors". Cancer Research. 40 (11): 3921–3927. PMID 7471043.
  31. ^ Sun Z, Zhang Z, Wang QQ, Liu JL (March 2022). "Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells". Cancer Research. 82 (6): 1013–1024. doi:10.1158/0008-5472.can-21-1707. PMC 9359733. PMID 35022212.
  32. ^ Whelan J, Smith T, Phear G, Rohatiner A, Lister A, Meuth M (February 1994). "Resistance to cytosine arabinoside in acute leukemia: the significance of mutations in CTP synthetase". Leukemia. 8 (2): 264–265. PMID 8309250.

Further reading edit

  • Veillette A, Davidson D (June 2014). "Immunology: When lymphocytes run out of steam". Nature. 510 (7504): 222–223. Bibcode:2014Natur.510..222V. doi:10.1038/nature13346. PMID 24870231. S2CID 4468136.

External links edit

April 16, 2024
synthetase, synthase, enzyme, involved, pyrimidine, biosynthesis, that, interconverts, synthaseidentifiersec, 2cas, 9023, 7databasesintenzintenz, viewbrendabrenda, entryexpasynicezyme, viewkeggkegg, entrymetacycmetabolic, pathwaypriamprofilepdb, structuresrcsb. CTP synthase is an enzyme EC 6 3 4 2 involved in pyrimidine biosynthesis that interconverts UTP and CTP 1 2 CTP synthaseIdentifiersEC no 6 3 4 2CAS no 9023 56 7DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteins Contents 1 Reaction mechanism 2 Isozymes 3 Structure 4 Regulation 5 Filaments 6 Clinical significance 7 See also 8 References 9 Further reading 10 External linksReaction mechanism editCTP cytidine triphosphate synthetase catalyzes the last committed step in pyrimidine nucleotide biosynthesis 3 ATP UTP glutamine ADP Pi CTP glutamateIt is the rate limiting enzyme for the synthesis of cytosine nucleotides from both the de novo and uridine salvage pathways 4 The reaction proceeds by the ATP dependent phosphorylation of UTP on the 4 oxygen atom making the 4 carbon electrophilic and vulnerable to reaction with ammonia 5 The source of the amino group in CTP is glutamine which is hydrolysed in a glutamine amidotransferase domain to produce ammonia This is then channeled through the interior of the enzyme to the synthetase domain 6 7 Here ammonia reacts with the intermediate 4 phosphoryl UTP 8 nbsp Isozymes editTwo isozymes with CTP synthase activity exist in humans encoded by the following genes CTPS CTP synthase 1 CTPS2 CTP synthase 2Structure edit nbsp Dimeric form of CTP synthase from Sulfolobus solfataricus PDB code 3NVA Chain A is depicted in blue and Chain B in green Active CTP synthase exists as a homotetrameric enzyme At low enzyme concentrations and in the absence of ATP and UTP CTP synthase exists as inactive monomer As enzyme concentration increases it polymerizes first to a dimer such as the form shown to the left and in the presence of ATP and UTP forms a tetramer 5 9 The enzyme contains two major domains responsible for the aminotransferase and synthase activity respectively The amidotransferase domains are located away from the tetramer interfaces and are not affected by the oligomeric state The ATP binding site and CTP binding site in the synthase domain are located at the tetramer interface It is for this reason that ATP and UTP are required for tetramerization 10 Regulation editCTP synthase is precisely regulated by the intracellular concentrations of CTP and UTP and both hCTPS1 and hCTPS2 have been seen to be maximally active at physiological concentrations of ATP GTP and glutamine 11 The activity of human CTPS1 isozyme has been demonstrated to be inhibited by phosphorylation 12 One major example of this is phosphorylation of the Ser 571 residue by glycogen synthase kinase 3 GSK3 in response to low serum conditions 13 Additionally Ser568 has been seen to be phosphorylated by casein kinase 1 inhibiting CTP synthase activity 11 CTP is also subject to various forms of allosteric regulation GTP acts as an allosteric activator that strongly promotes the hydrolysis of glutamine but is also inhibiting to glutamine dependent CTP formation at high concentrations 14 This acts to balance the relative amounts of purine and pyrimidine nucleotides The reaction product CTP also serves as an allosteric inhibitor The triphosphate binding site overlaps with that of UTP but the nucleoside moiety of CTP binds in an alternative pocket opposite the binding site for UTP 15 CTP synthase levels have been shown to be dependent on levels of the transcription factor Myc In turn CTP synthase activity is required for Myc related phenotypes 16 The glutamine analog DON has also been seen to act as an irreversible inhibitor and has been used as an anti cancer agent 17 Filaments editCTP synthase has been reported to form filaments in several different organisms These include bacteria C crescentus 18 yeast S cerevisiae 19 fruit flies D melanogaster 20 and human cells 21 These filamentous structures have been referred to as cytoplasmic rods and rings 22 cytoophidia from the Greek cyto meaning cell and ophidium meaning serpent due to the structures morphology or simply CTP synthase filaments It has been shown that filamentation downregulates or upregulates CTP synthase activity depending on the species 23 24 25 26 27 In Drosophila only one of the CTP synthase isoform forms the filament 28 Since the discovery of this novel mode of enzyme regulation in CTP synthase multiple other enzymes have been shown to exhibit similar characteristics suggesting that this is an important and well conserved strategy for enzymatic regulation 29 CTP synthase remains a model enzyme for the study of filament formation Clinical significance editUpregulated CTP synthase activity has been widely seen in human and rodent tumors 30 Evidence from fly models 16 and human cancer cells 31 suggests that Myc dependent cell growth may be more susceptible to suppression of CTP synthase activity Mutations in the CTP synthase have been seen to confer resistance to cytotoxic drugs such as cytosine arabinoside ara C in a Chinese hamster ovary CHO cell model of leukemia though such mutations were not found in human patients with ara C resistance 32 See also editPyrimidine biosynthesisReferences edit Lieberman I October 1956 Enzymatic amination of uridine triphosphate to cytidine triphosphate The Journal of Biological Chemistry 222 2 765 775 doi 10 1016 S0021 9258 20 89934 7 PMID 13367044 Long CW Levitzki A Koshland DE January 1970 The subunit structure and subunit interactions of cytidine triphosphate synthetase The Journal of Biological Chemistry 245 1 80 87 doi 10 1016 S0021 9258 18 63424 6 PMID 5411547 Koshland DE Levitzki A 1974 CTP Synthetase and Related Enzymes In Boyer PD ed The Enzymes 3rd ed New York Academic Press pp 539 59 ISBN 978 0 12 122710 4 van Kuilenburg AB Meinsma R Vreken P Waterham HR van Gennip AH 2000 Isoforms of human CTP synthetase Purine and Pyrimidine Metabolism in Man X Advances in Experimental Medicine and Biology Vol 486 pp 257 261 doi 10 1007 0 306 46843 3 50 ISBN 978 0 306 46515 4 PMID 11783495 a b von der Saal W Anderson PM Villafranca JJ December 1985 Mechanistic investigations of Escherichia coli cytidine 5 triphosphate synthetase Detection of an intermediate by positional isotope exchange experiments The Journal of Biological Chemistry 260 28 14993 14997 doi 10 1016 S0021 9258 18 95692 9 PMID 2933396 Levitzki A Koshland DE August 1971 Cytidine triphosphate synthetase Covalent intermediates and mechanisms of action Biochemistry 10 18 3365 3371 doi 10 1021 bi00794a008 PMID 4940761 Endrizzi JA Kim H Anderson PM Baldwin EP June 2004 Crystal structure of Escherichia coli cytidine triphosphate synthetase a nucleotide regulated glutamine amidotransferase ATP dependent amidoligase fusion protein and homologue of anticancer and antiparasitic drug targets Biochemistry 43 21 6447 6463 doi 10 1021 bi0496945 PMC 2891762 PMID 15157079 Lewis DA Villafranca JJ October 1989 Investigation of the mechanism of CTP synthetase using rapid quench and isotope partitioning methods Biochemistry 28 21 8454 8459 doi 10 1021 bi00447a027 PMID 2532543 Anderson PM June 1983 CTP synthetase from Escherichia coli an improved purification procedure and characterization of hysteretic and enzyme concentration effects on kinetic properties Biochemistry 22 13 3285 3292 doi 10 1021 bi00282a038 PMID 6349684 Lauritsen I Willemoes M Jensen KF Johansson E Harris P February 2011 Structure of the dimeric form of CTP synthase from Sulfolobus solfataricus Acta Crystallographica Section F Structural Biology and Crystallization Communications 67 Pt 2 201 208 doi 10 1107 S1744309110052334 PMC 3034608 PMID 21301086 a b Kassel KM Higgins MJ Hines M Graves LM October 2010 Regulation of human cytidine triphosphate synthetase 2 by phosphorylation The Journal of Biological Chemistry 285 44 33727 33736 doi 10 1074 jbc M110 178566 PMC 2962471 PMID 20739275 Carman GM Kersting MC February 2004 Phospholipid synthesis in yeast regulation by phosphorylation Biochemistry and Cell Biology 82 1 62 70 doi 10 1139 o03 064 PMID 15052328 Higgins MJ Graves PR Graves LM October 2007 Regulation of human cytidine triphosphate synthetase 1 by glycogen synthase kinase 3 The Journal of Biological Chemistry 282 40 29493 29503 doi 10 1074 jbc M703948200 PMID 17681942 Lunn FA MacDonnell JE Bearne SL January 2008 Structural requirements for the activation of Escherichia coli CTP synthase by the allosteric effector GTP are stringent but requirements for inhibition are lax The Journal of Biological Chemistry 283 4 2010 2020 doi 10 1074 jbc M707803200 PMID 18003612 Endrizzi JA Kim H Anderson PM Baldwin EP October 2005 Mechanisms of product feedback regulation and drug resistance in cytidine triphosphate synthetases from the structure of a CTP inhibited complex Biochemistry 44 41 13491 13499 doi 10 1021 bi051282o PMC 2891682 PMID 16216072 a b Aughey GN Grice SJ Liu JL February 2016 The Interplay between Myc and CTP Synthase in Drosophila PLOS Genetics 12 2 e1005867 doi 10 1371 journal pgen 1005867 PMC 4759343 PMID 26889675 Ahluwalia GS Grem JL Hao Z Cooney DA 1990 Metabolism and action of amino acid analog anti cancer agents Pharmacology amp Therapeutics 46 2 243 271 doi 10 1016 0163 7258 90 90094 I PMID 2108451 Ingerson Mahar M Briegel A Werner JN Jensen GJ Gitai Z August 2010 The metabolic enzyme CTP synthase forms cytoskeletal filaments Nature Cell Biology 12 8 739 746 doi 10 1038 ncb2087 PMC 3210567 PMID 20639870 Noree C Sato BK Broyer RM Wilhelm JE August 2010 Identification of novel filament forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster The Journal of Cell Biology 190 4 541 551 doi 10 1083 jcb 201003001 PMC 2928026 PMID 20713603 Liu JL May 2010 Intracellular compartmentation of CTP synthase in Drosophila Journal of Genetics and Genomics Yi Chuan Xue Bao 37 5 281 296 doi 10 1016 S1673 8527 09 60046 1 PMID 20513629 S2CID 206173864 Chen K Zhang J Tastan OY Deussen ZA Siswick MY Liu JL September 2011 Glutamine analogs promote cytoophidium assembly in human and Drosophila cells Journal of Genetics and Genomics Yi Chuan Xue Bao 38 9 391 402 doi 10 1016 j jgg 2011 08 004 PMID 21930098 Carcamo WC Satoh M Kasahara H Terada N Hamazaki T Chan JY et al 2011 Induction of cytoplasmic rods and rings structures by inhibition of the CTP and GTP synthetic pathway in mammalian cells PLOS ONE 6 12 e29690 Bibcode 2011PLoSO 629690C doi 10 1371 journal pone 0029690 PMC 3248424 PMID 22220215 Lynch EM Hicks DR Shepherd M Endrizzi JA Maker A Hansen JM et al June 2017 Human CTP synthase filament structure reveals the active enzyme conformation Nature Structural amp Molecular Biology 24 6 507 514 doi 10 1038 nsmb 3407 PMC 5472220 PMID 28459447 Barry RM Bitbol AF Lorestani A Charles EJ Habrian CH Hansen JM et al July 2014 Large scale filament formation inhibits the activity of CTP synthetase eLife 3 e03638 doi 10 7554 eLife 03638 PMC 4126345 PMID 25030911 Aughey GN Grice SJ Shen QJ Xu Y Chang CC Azzam G et al October 2014 Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism Biology Open 3 11 1045 1056 doi 10 1242 bio 201410165 PMC 4232762 PMID 25326513 Noree C Monfort E Shiau AK Wilhelm JE August 2014 Common regulatory control of CTP synthase enzyme activity and filament formation Molecular Biology of the Cell 25 15 2282 2290 doi 10 1091 mbc E14 04 0912 PMC 4116302 PMID 24920825 Barry RM Gitai Z December 2011 Self assembling enzymes and the origins of the cytoskeleton Current Opinion in Microbiology 14 6 704 711 doi 10 1016 j mib 2011 09 015 PMC 3234109 PMID 22014508 Azzam G Liu JL February 2013 Only one isoform of Drosophila melanogaster CTP synthase forms the cytoophidium PLOS Genetics 9 2 e1003256 doi 10 1371 journal pgen 1003256 PMC 3573105 PMID 23459760 Aughey GN Liu JL 2015 Metabolic regulation via enzyme filamentation Critical Reviews in Biochemistry and Molecular Biology 51 4 282 293 doi 10 3109 10409238 2016 1172555 PMC 4915340 PMID 27098510 Kizaki H Williams JC Morris HP Weber G November 1980 Increased cytidine 5 triphosphate synthetase activity in rat and human tumors Cancer Research 40 11 3921 3927 PMID 7471043 Sun Z Zhang Z Wang QQ Liu JL March 2022 Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC Overexpressing Cancer Cells Cancer Research 82 6 1013 1024 doi 10 1158 0008 5472 can 21 1707 PMC 9359733 PMID 35022212 Whelan J Smith T Phear G Rohatiner A Lister A Meuth M February 1994 Resistance to cytosine arabinoside in acute leukemia the significance of mutations in CTP synthetase Leukemia 8 2 264 265 PMID 8309250 Further reading editVeillette A Davidson D June 2014 Immunology When lymphocytes run out of steam Nature 510 7504 222 223 Bibcode 2014Natur 510 222V doi 10 1038 nature13346 PMID 24870231 S2CID 4468136 External links editCTP synthetase at the U S National Library of Medicine Medical Subject Headings MeSH Portal nbsp Biology Retrieved from https en wikipedia org w index php title CTP synthetase amp oldid 1173517079, wikipedia, wiki, book, books, library,

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