PDBsum entry 1vcm

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protein links
Ligase PDB id
Protein chain
531 a.a. *
Waters ×312
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structure of t.Th. Hb8 ctp synthetase
Structure: Ctp synthetase. Chain: a. Engineered: yes
Source: Thermus thermophilus. Organism_taxid: 274. Gene: hb8. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
2.35Å     R-factor:   0.235     R-free:   0.279
Authors: M.Goto,Riken Structural Genomics/proteomics Initiative (Rsgi
Key ref:
M.Goto et al. (2004). Crystal structures of CTP synthetase reveal ATP, UTP, and glutamine binding sites. Structure, 12, 1413-1423. PubMed id: 15296735 DOI: 10.1016/j.str.2004.05.013
10-Mar-04     Release date:   31-Aug-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q5SIA8  (PYRG_THET8) -  CTP synthase
550 a.a.
531 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Ctp synthase (glutamine hydrolyzing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + UTP + L-glutamine = ADP + phosphate + CTP + L-glutamate
+ L-glutamine
+ phosphate
+ L-glutamate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     'de novo' CTP biosynthetic process   3 terms 
  Biochemical function     nucleotide binding     4 terms  


DOI no: 10.1016/j.str.2004.05.013 Structure 12:1413-1423 (2004)
PubMed id: 15296735  
Crystal structures of CTP synthetase reveal ATP, UTP, and glutamine binding sites.
M.Goto, R.Omi, N.Nakagawa, I.Miyahara, K.Hirotsu.
CTP synthetase (CTPs) catalyzes the last step in CTP biosynthesis, in which ammonia generated at the glutaminase domain reacts with the ATP-phosphorylated UTP at the synthetase domain to give CTP. Glutamine hydrolysis is active in the presence of ATP and UTP and is stimulated by the addition of GTP. We report the crystal structures of Thermus thermophilus HB8 CTPs alone, CTPs with 3SO4(2-), and CTPs with glutamine. The enzyme is folded into a homotetramer with a cross-shaped structure. Based on the binding mode of sulfate anions to the synthetase site, ATP and UTP are computer modeled into CTPs with a geometry favorable for the reaction. Glutamine bound to the glutaminase domain is situated next to the triad of Glu-His-Cys as a catalyst and a water molecule. Structural information provides an insight into the conformational changes associated with the binding of ATP and UTP and the formation of the GTP binding site.
  Selected figure(s)  
Figure 8.
Figure 8. Putative Conformational Change upon Binding of ATP and UTPThe glutaminase domain (brown) is rotated toward the synthetase domain (blue) on the graphics to form a computer model of the compact molecule in the closed form. The consensus sequence (green) specific for GTP on the glutaminase domain approaches that (green) on the synthetase domain to form a binding site for GTP. ATP and UTP modeled into the closed form are drawn in red.
  The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1413-1423) copyright 2004.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21254152 J.L.Liu (2011).
The enigmatic cytoophidium: Compartmentation of CTP synthase via filament formation.
  Bioessays, 33, 159-164.  
18003612 F.A.Lunn, J.E.Macdonnell, and S.L.Bearne (2008).
Structural Requirements for the Activation of Escherichia coli CTP Synthase by the Allosteric Effector GTP Are Stringent, but Requirements for Inhibition Are Lax.
  J Biol Chem, 283, 2010-2020.  
18597481 M.Morar, A.A.Hoskins, J.Stubbe, and S.E.Ealick (2008).
Formylglycinamide ribonucleotide amidotransferase from Thermotoga maritima: structural insights into complex formation.
  Biochemistry, 47, 7816-7830.
PDB code: 3d54
18439916 Y.F.Chang, and G.M.Carman (2008).
CTP synthetase and its role in phospholipid synthesis in the yeast Saccharomyces cerevisiae.
  Prog Lipid Res, 47, 333-339.  
17331943 A.Fijolek, A.Hofer, and L.Thelander (2007).
Expression, purification, characterization, and in vivo targeting of trypanosome CTP synthetase for treatment of African sleeping sickness.
  J Biol Chem, 282, 11858-11865.  
17189248 M.G.Choi, and G.M.Carman (2007).
Phosphorylation of human CTP synthetase 1 by protein kinase A: identification of Thr455 as a major site of phosphorylation.
  J Biol Chem, 282, 5367-5377.  
17681942 M.J.Higgins, P.R.Graves, and L.M.Graves (2007).
Regulation of human cytidine triphosphate synthetase 1 by glycogen synthase kinase 3.
  J Biol Chem, 282, 29493-29503.  
17600152 O.Braun, M.Knipp, S.Chesnov, and M.Vasák (2007).
Specific reactions of S-nitrosothiols with cysteine hydrolases: A comparative study between dimethylargininase-1 and CTP synthetase.
  Protein Sci, 16, 1522-1534.  
17951049 S.Mouilleron, and B.Golinelli-Pimpaneau (2007).
Conformational changes in ammonia-channeling glutamine amidotransferases.
  Curr Opin Struct Biol, 17, 653-664.  
17463002 Y.F.Chang, S.S.Martin, E.P.Baldwin, and G.M.Carman (2007).
Phosphorylation of human CTP synthetase 1 by protein kinase C: identification of Ser(462) and Thr(455) as major sites of phosphorylation.
  J Biol Chem, 282, 17613-17622.  
  16820675 P.Kursula, S.Flodin, M.Ehn, M.Hammarström, H.Schüler, P.Nordlund, and P.Stenmark (2006).
Structure of the synthetase domain of human CTP synthetase, a target for anticancer therapy.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 613-617.
PDB codes: 2c5m 2vo1
16179339 G.S.Han, A.Sreenivas, M.G.Choi, Y.F.Chang, S.S.Martin, E.P.Baldwin, and G.M.Carman (2005).
Expression of Human CTP synthetase in Saccharomyces cerevisiae reveals phosphorylation by protein kinase A.
  J Biol Chem, 280, 38328-38336.  
16216072 J.A.Endrizzi, H.Kim, P.M.Anderson, and E.P.Baldwin (2005).
Mechanisms of product feedback regulation and drug resistance in cytidine triphosphate synthetases from the structure of a CTP-inhibited complex.
  Biochemistry, 44, 13491-13499.
PDB code: 2ad5
15670165 M.Willemoës, A.Mølgaard, E.Johansson, and J.Martinussen (2005).
Lid L11 of the glutamine amidotransferase domain of CTP synthase mediates allosteric GTP activation of glutaminase activity.
  FEBS J, 272, 856-864.  
7797479 W.L.Yang, and G.M.Carman (1995).
Phosphorylation of CTP synthetase from Saccharomyces cerevisiae by protein kinase C.
  J Biol Chem, 270, 14983-14988.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.