PDBsum entry 1ce8

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protein ligands metals Protein-protein interface(s) links
Ligase imp PDB id
Protein chains
1058 a.a. *
379 a.a. *
ADP ×8
PO4 ×4
ORN ×8
IMP ×4
NET ×4
__K ×28
_MN ×12
_CL ×12
Waters ×4037
* Residue conservation analysis
PDB id:
Name: Ligase imp
Title: Carbamoyl phosphate synthetase from escherichis coli with co with the allosteric ligand imp
Structure: Protein (carbamoyl-phosphate synthase). Chain: a, c, e, g. Engineered: yes. Other_details: long chain. Protein (carbamoyl-phosphate synthase). Chain: b, d, f, h. Engineered: yes. Other_details: short chain
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Hetero-Tetramer (from PDB file)
2.10Å     R-factor:   0.192     R-free:   0.250
Authors: J.B.Thoden,F.M.Raushel,H.M.Holden
Key ref:
J.B.Thoden et al. (1999). The binding of inosine monophosphate to Escherichia coli carbamoyl phosphate synthetase. J Biol Chem, 274, 22502-22507. PubMed id: 10428826 DOI: 10.1074/jbc.274.32.22502
18-Mar-99     Release date:   26-Jul-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00968  (CARB_ECOLI) -  Carbamoyl-phosphate synthase large chain
1073 a.a.
1058 a.a.*
Protein chains
Pfam   ArchSchema ?
P0A6F1  (CARA_ECOLI) -  Carbamoyl-phosphate synthase small chain
382 a.a.
379 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.  - Carbamoyl-phosphate synthase (glutamine-hydrolyzing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Pyrimidine Biosynthesis
      Reaction: 2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
2 × ATP
Bound ligand (Het Group name = ORN)
matches with 90.00% similarity
+ HCO(3)(-)
+ H(2)O
2 × ADP
Bound ligand (Het Group name = ADP)
corresponds exactly
Bound ligand (Het Group name = PO4)
corresponds exactly
+ L-glutamate
+ carbamoyl phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     metabolic process   13 terms 
  Biochemical function     catalytic activity     9 terms  


DOI no: 10.1074/jbc.274.32.22502 J Biol Chem 274:22502-22507 (1999)
PubMed id: 10428826  
The binding of inosine monophosphate to Escherichia coli carbamoyl phosphate synthetase.
J.B.Thoden, F.M.Raushel, G.Wesenberg, H.M.Holden.
Carbamoyl phosphate synthetase (CPS) from Escherichia coli catalyzes the formation of carbamoyl phosphate, which is subsequently employed in both the pyrimidine and arginine biosynthetic pathways. The reaction mechanism is known to proceed through at least three highly reactive intermediates: ammonia, carboxyphosphate, and carbamate. In keeping with the fact that the product of CPS is utilized in two competing metabolic pathways, the enzyme is highly regulated by a variety of effector molecules including potassium and ornithine, which function as activators, and UMP, which acts as an inhibitor. IMP is also known to bind to CPS but the actual effect of this ligand on the activity of the enzyme is dependent upon both temperature and assay conditions. Here we describe the three-dimensional architecture of CPS with bound IMP determined and refined to 2.1 A resolution. The nucleotide is situated at the C-terminal portion of a five-stranded parallel beta-sheet in the allosteric domain formed by Ser(937) to Lys(1073). Those amino acid side chains responsible for anchoring the nucleotide to the polypeptide chain include Lys(954), Thr(974), Thr(977), Lys(993), Asn(1015), and Thr(1017). A series of hydrogen bonds connect the IMP-binding pocket to the active site of the large subunit known to function in the phosphorylation of the unstable intermediate, carbamate. This structural analysis reveals, for the first time, the detailed manner in which CPS accommodates nucleotide monophosphate effector molecules within the allosteric domain.
  Selected figure(s)  
Figure 3.
Fig. 3. The IMP binding pocket. Panel a, a close-up view of those amino acid residues located within approximately 5 Å of atoms of the IMP. Panel b, a cartoon of potential hydrogen bonds between the ligand and the protein, as indicated by the dashed lines.
Figure 4.
Fig. 4. Superposition of the CPS allosteric binding pockets with bound IMP or glutamine/inorganic phosphate. The model described in this report is shown in black, whereas the structure of CPS complexed with glutamine and inorganic phosphate, as described by Thoden et al. (2), is displayed in red. Note the nearly exact correspondence between the inorganic phosphate and the phosphoryl moiety of the nucleotide.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (1999, 274, 22502-22507) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18793461 C.A.Bottoms, and D.Xu (2008).
Wanted: unique names for unique atom positions. PDB-wide analysis of diastereotopic atom names of small molecules containing diphosphate.
  BMC Bioinformatics, 9, S16.  
17209549 J.L.Johnson, J.K.West, A.D.Nelson, and G.D.Reinhart (2007).
Resolving the fluorescence response of Escherichia coli carbamoyl phosphate synthetase: mapping intra- and intersubunit conformational changes.
  Biochemistry, 46, 387-397.  
15322282 J.B.Thoden, X.Huang, J.Kim, F.M.Raushel, and H.M.Holden (2004).
Long-range allosteric transitions in carbamoyl phosphate synthetase.
  Protein Sci, 13, 2398-2405.
PDB code: 1t36
15128434 V.Serre, B.Penverne, J.L.Souciet, S.Potier, H.Guy, D.Evans, P.Vicart, and G.Hervé (2004).
Integrated allosteric regulation in the S. cerevisiae carbamylphosphate synthetase - aspartate transcarbamylase multifunctional protein.
  BMC Biochem, 5, 6.  
11119647 M.M.Horvath, and N.V.Grishin (2001).
The C-terminal domain of HPII catalase is a member of the type I glutamine amidotransferase superfamily.
  Proteins, 42, 230-236.  
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