PDBsum entry 1qd1

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Transferase PDB id
Protein chains
319 a.a. *
FON ×2
GOL ×2
Waters ×771
* Residue conservation analysis
PDB id:
Name: Transferase
Title: The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase.
Structure: Formiminotransferase-cyclodeaminase. Chain: a, b. Fragment: formiminotransferase domain. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
1.70Å     R-factor:   0.191     R-free:   0.213
Authors: D.Kohls,T.Sulea,E.Purisima,R.E.Mackenzie,A.Vrielink
Key ref:
D.Kohls et al. (2000). The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme. Structure, 8, 35-46. PubMed id: 10673422 DOI: 10.1016/S0969-2126(00)00078-2
08-Jul-99     Release date:   12-Jan-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P53603  (FTCD_PIG) -  Formimidoyltransferase-cyclodeaminase
541 a.a.
319 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.  - Glutamate formimidoyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Histidine Catabolism
1. 5-formimidoyltetrahydrofolate + L-glutamate = tetrahydrofolate + N-formimidoyl-L-glutamate
2. 5-formyltetrahydrofolate + L-glutamate = tetrahydrofolate + N-formyl- L-glutamate
Bound ligand (Het Group name = FON)
matches with 94.29% similarity
+ L-glutamate
= tetrahydrofolate
+ N-formimidoyl-L-glutamate
Bound ligand (Het Group name = FON)
corresponds exactly
+ L-glutamate
= tetrahydrofolate
+ N-formyl- L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
   Enzyme class 3: E.C.  - Formimidoyltetrahydrofolate cyclodeaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: 5-formimidoyltetrahydrofolate = 5,10-methenyltetrahydrofolate + NH3
Bound ligand (Het Group name = FON)
matches with 97.06% similarity
+ NH(3)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     transferase activity     2 terms  


DOI no: 10.1016/S0969-2126(00)00078-2 Structure 8:35-46 (2000)
PubMed id: 10673422  
The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme.
D.Kohls, T.Sulea, E.O.Purisima, R.E.MacKenzie, A.Vrielink.
BACKGROUND: The bifunctional enzyme formiminotransferase-cyclodeaminase (FTCD) contains two active sites at different positions on the protein structure. The enzyme binds a gamma-linked polyglutamylated form of the tetrahydrofolate substrate and channels the product of the transferase reaction from the transferase active site to the cyclodeaminase active site. Structural studies of this bifunctional enzyme and its monofunctional domains will provide insight into the mechanism of substrate channeling and the two catalytic reactions. RESULTS: The crystal structure of the formiminotransferase (FT) domain of FTCD has been determined in the presence of a product analog, folinic acid. The overall structure shows that the FT domain comprises two subdomains that adopt a novel alpha/beta fold. Inspection of the folinic acid binding site reveals an electrostatic tunnel traversing the width of the molecule. The distribution of charged residues in the tunnel provides insight into the possible mode of substrate binding and channeling. The electron density reveals that the non-natural stereoisomer, (6R)-folinic acid, binds to the protein; this observation suggests a mechanism for product release. In addition, a single molecule of glycerol is bound to the enzyme and indicates a putative binding site for formiminoglutamate. CONCLUSIONS: The structure of the FT domain in the presence of folinic acid reveals a possible novel mechanism for substrate channeling. The position of the folinic acid and a bound glycerol molecule near to the sidechain of His82 suggests that this residue may act as the catalytic base required for the formiminotransferase mechanism.
  Selected figure(s)  
Figure 1.
Figure 1. Chemical structures for the compounds discussed in this study. (a) The reactions catalyzed by formiminotransferase-cyclodeaminase. The first reaction is carried out by the formiminotransferase (FT) domain to produce N5-formiminotetrahydrofolate. The second reaction is carried out by the cyclodeaminase (CD) domain and results in the formation of the final product, N5,N10-methenyltetrahydrofolate. The atom numbering for the ligand used in the text is shown. (b) The product analog, folinic acid, cocrystallized with the FT domain.
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 35-46) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17342452 C.Köhler, O.M.Andersen, A.Diehl, G.Krause, P.Schmieder, and H.Oschkinat (2006).
The solution structure of the core of mesoderm development (MESD), a chaperone for members of the LDLR-family.
  J Struct Funct Genomics, 7, 131-138.
PDB code: 2i9s
16447290 M.P.Manns, and A.Vogel (2006).
Autoimmune hepatitis, from mechanisms to therapy.
  Hepatology, 43, S132-S144.  
15936248 A.Nzila, S.A.Ward, K.Marsh, P.F.Sims, and J.E.Hyde (2005).
Comparative folate metabolism in humans and malaria parasites (part II): activities as yet untargeted or specific to Plasmodium.
  Trends Parasitol, 21, 334-339.  
15651027 Q.Xu, R.Schwarzenbacher, D.McMullan, P.Abdubek, E.Ambing, T.Biorac, J.M.Canaves, H.J.Chiu, X.Dai, A.M.Deacon, M.DiDonato, M.A.Elsliger, A.Godzik, C.Grittini, S.K.Grzechnik, E.Hampton, M.Hornsby, L.Jaroszewski, H.E.Klock, E.Koesema, A.Kreusch, P.Kuhn, S.A.Lesley, I.Levin, M.D.Miller, A.Morse, K.Moy, J.Ouyang, R.Page, K.Quijano, R.Reyes, A.Robb, E.Sims, G.Spraggon, R.C.Stevens, H.van den Bedem, J.Velasquez, J.Vincent, F.von Delft, X.Wang, B.West, A.White, G.Wolf, O.Zagnitko, K.O.Hodgson, J.Wooley, and I.A.Wilson (2005).
Crystal structure of a formiminotetrahydrofolate cyclodeaminase (TM1560) from Thermotoga maritima at 2.80 A resolution reveals a new fold.
  Proteins, 58, 976-981.
PDB code: 1o5h
14987745 K.Béland, P.Lapierre, G.Marceau, and F.Alvarez (2004).
Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection.
  J Autoimmun, 22, 159-166.  
15272307 Y.Mao, N.K.Vyas, M.N.Vyas, D.H.Chen, S.J.Ludtke, W.Chiu, and F.A.Quiocho (2004).
Structure of the bifunctional and Golgi-associated formiminotransferase cyclodeaminase octamer.
  EMBO J, 23, 2963-2971.
PDB code: 1tt9
12912903 D.Leys, J.Basran, and N.S.Scrutton (2003).
Channelling and formation of 'active' formaldehyde in dimethylglycine oxidase.
  EMBO J, 22, 4038-4048.
PDB codes: 1pj5 1pj6 1pj7
12815595 J.F.Hilton, K.E.Christensen, D.Watkins, B.A.Raby, Y.Renaud, la Luna, X.Estivill, R.E.MacKenzie, T.J.Hudson, and D.S.Rosenblatt (2003).
The molecular basis of glutamate formiminotransferase deficiency.
  Hum Mutat, 22, 67-73.  
12438316 T.F.Fu, J.N.Scarsdale, G.Kazanina, V.Schirch, and H.T.Wright (2003).
Location of the pteroylpolyglutamate-binding site on rabbit cytosolic serine hydroxymethyltransferase.
  J Biol Chem, 278, 2645-2653.
PDB code: 1ls3
11953756 J.Sivaraman, V.Sauvé, R.Larocque, E.A.Stura, J.D.Schrag, M.Cygler, and A.Matte (2002).
Structure of the 16S rRNA pseudouridine synthase RsuA bound to uracil and UMP.
  Nat Struct Biol, 9, 353-358.
PDB codes: 1ksk 1ksl 1ksv
11395405 X.Huang, H.M.Holden, and F.M.Raushel (2001).
Channeling of substrates and intermediates in enzyme-catalyzed reactions.
  Annu Rev Biochem, 70, 149-180.  
11080639 F.Tête-Favier, D.Cobessi, S.Boschi-Muller, S.Azza, G.Branlant, and A.Aubry (2000).
Crystal structure of the Escherichia coli peptide methionine sulphoxide reductase at 1.9 A resolution.
  Structure, 8, 1167-1178.
PDB code: 1ff3
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.