spacer
spacer
Go to PDB code: 
protein ligands Protein-protein interface(s) links
Transferase(formyl) PDB id
1cde
Jmol
Contents
Protein chains
209 a.a. *
Ligands
GAR ×4
DZF ×4
* Residue conservation analysis
PDB id:
1cde
Name: Transferase(formyl)
Title: Structures of apo and complexed escherichia coli glycinamide ribonucleotide transformylase
Structure: Phosphoribosyl-glycinamide formyltransferase. Chain: a, b, c, d. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562.
Resolution:
2.50Å     R-factor:   0.250    
Authors: R.J.Almassy,C.A.Janson,C.-C.Kan,Z.Hostomska
Key ref: R.J.Almassy et al. (1992). Structures of apo and complexed Escherichia coli glycinamide ribonucleotide transformylase. Proc Natl Acad Sci U S A, 89, 6114-6118. PubMed id: 1631098 DOI: 10.1073/pnas.89.13.6114
Date:
15-May-92     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P08179  (PUR3_ECOLI) -  Phosphoribosylglycinamide formyltransferase
Seq:
Struc: 		212 a.a.
209 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.1.2.2  - Phosphoribosylglycinamide formyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Purine Biosynthesis (early stages)
      Reaction: 10-formyltetrahydrofolate + N1-(5-phospho-D-ribosyl)glycinamide = tetrahydrofolate + N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide
10-formyltetrahydrofolate
 +
N(1)-(5-phospho-D-ribosyl)glycinamide
Bound ligand (Het Group name = GAR)
corresponds exactly 		=
tetrahydrofolate
Bound ligand (Het Group name = DZF)
matches with 93.00% similarity 		+ N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     biosynthetic process   3 terms 
  Biochemical function     transferase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.89.13.6114 Proc Natl Acad Sci U S A 89:6114-6118 (1992)
PubMed id: 1631098  
 
 
Structures of apo and complexed Escherichia coli glycinamide ribonucleotide transformylase.
R.J.Almassy, C.A.Janson, C.C.Kan, Z.Hostomska.
 
  ABSTRACT  
 
The three-dimensional structure of phosphoribosylglycinamide formyltransferase (10-formyltetrahydrofolate:5'-phosphoribosylglycinamide formyltransferase, EC 2.1.2.2) has been solved both as an apoenzyme at 2.8-A resolution and as a ternary complex with the substrate glycinamide ribonucleotide and a folate inhibitor at 2.5-A resolution. The structure is a modified doubly wound alpha/beta sheet with flexibility in the active site, including a disordered loop in the apo structure, which is ordered in the ternary complex structure. This enzyme is a target for anti-cancer therapy and now for structure-based drug design.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18848533 S.A.Krupenko (2009).
FDH: an aldehyde dehydrogenase fusion enzyme in folate metabolism.
  Chem Biol Interact, 178, 84-93.  
17932934 S.Wong, and M.P.Jacobson (2008).
Conformational selection in silico: loop latching motions and ligand binding in enzymes.
  Proteins, 71, 153-164.  
18712276 Y.Zhang, M.Morar, and S.E.Ealick (2008).
Structural biology of the purine biosynthetic pathway.
  Cell Mol Life Sci, 65, 3699-3724.  
17198385 W.Manieri, M.E.Moore, M.B.Soellner, P.Tsang, and C.A.Caperelli (2007).
Human glycinamide ribonucleotide transformylase: active site mutants as mechanistic probes.
  Biochemistry, 46, 156-163.  
16966397 J.W.Teo, P.Thayalan, D.Beer, A.S.Yap, M.Nanjundappa, X.Ngew, J.Duraiswamy, S.Liung, V.Dartois, M.Schreiber, S.Hasan, M.Cynamon, N.S.Ryder, X.Yang, B.Weidmann, K.Bracken, T.Dick, and K.Mukherjee (2006).
Peptide deformylase inhibitors as potent antimycobacterial agents.
  Antimicrob Agents Chemother, 50, 3665-3673.  
15807526 P.Z.Gatzeva-Topalova, A.P.May, and M.C.Sousa (2005).
Crystal structure and mechanism of the Escherichia coli ArnA (PmrI) transformylase domain. An enzyme for lipid A modification with 4-amino-4-deoxy-L-arabinose and polymyxin resistance.
  Biochemistry, 44, 5328-5338.
PDB code: 1yrw
14500878 S.G.Lee, S.Lutz, and S.J.Benkovic (2003).
On the structural and functional modularity of glycinamide ribonucleotide formyltransferases.
  Protein Sci, 12, 2206-2214.  
12042875 C.A.Voigt, C.Martinez, Z.G.Wang, S.L.Mayo, and F.H.Arnold (2002).
Protein building blocks preserved by recombination.
  Nat Struct Biol, 9, 553-558.  
11604542 D.Morikis, A.H.Elcock, P.A.Jennings, and J.A.McCammon (2001).
Native-state conformational dynamics of GART: a regulatory pH-dependent coil-helix transition examined by electrostatic calculations.
  Protein Sci, 10, 2363-2378.  
11604543 D.Morikis, A.H.Elcock, P.A.Jennings, and J.A.McCammon (2001).
Proton transfer dynamics of GART: the pH-dependent catalytic mechanism examined by electrostatic calculations.
  Protein Sci, 10, 2379-2392.  
10966471 M.Ibba, and D.Soll (2000).
Aminoacyl-tRNA synthesis.
  Annu Rev Biochem, 69, 617-650.  
10694387 S.Gite, Y.Li, V.Ramesh, and U.L.RajBhandary (2000).
Escherichia coli methionyl-tRNA formyltransferase: role of amino acids conserved in the linker region and in the C-terminal domain on the specific recognition of the initiator tRNA.
  Biochemistry, 39, 2218-2226.  
  11006546 T.J.Kappock, S.E.Ealick, and J.Stubbe (2000).
Modular evolution of the purine biosynthetic pathway.
  Curr Opin Chem Biol, 4, 567-572.  
10944351 V.M.Reyes, S.E.Greasley, E.A.Stura, G.P.Beardsley, and I.A.Wilson (2000).
Crystallization and preliminary crystallographic investigations of avian 5-aminoimidazole-4-carboxamide ribonucleotide transformylase-inosine monophosphate cyclohydrolase expressed in Escherichia coli.
  Acta Crystallogr D Biol Crystallogr, 56, 1051-1054.  
  10508786 C.Li, T.J.Kappock, J.Stubbe, T.M.Weaver, and S.E.Ealick (1999).
X-ray crystal structure of aminoimidazole ribonucleotide synthetase (PurM), from the Escherichia coli purine biosynthetic pathway at 2.5 A resolution.
  Structure, 7, 1155-1166.
PDB code: 1cli
  10574791 I.I.Mathews, T.J.Kappock, J.Stubbe, and S.E.Ealick (1999).
Crystal structure of Escherichia coli PurE, an unusual mutase in the purine biosynthetic pathway.
  Structure, 7, 1395-1406.
PDB codes: 1d7a 1qcz
10097076 M.Ostermeier, A.E.Nixon, J.H.Shim, and S.J.Benkovic (1999).
Combinatorial protein engineering by incremental truncation.
  Proc Natl Acad Sci U S A, 96, 3562-3567.  
10606510 S.E.Greasley, M.M.Yamashita, H.Cai, S.J.Benkovic, D.L.Boger, and I.A.Wilson (1999).
New insights into inhibitor design from the crystal structure and NMR studies of Escherichia coli GAR transformylase in complex with beta-GAR and 10-formyl-5,8,10-trideazafolic acid.
  Biochemistry, 38, 16783-16793.
PDB codes: 1c2t 1c3e
9927661 V.Ramesh, C.Mayer, M.R.Dyson, S.Gite, and U.L.RajBhandary (1999).
Induced fit of a peptide loop of methionyl-tRNA formyltransferase triggered by the initiator tRNA substrate.
  Proc Natl Acad Sci U S A, 96, 875-880.  
9843487 E.Schmitt, M.Panvert, S.Blanquet, and Y.Mechulam (1998).
Crystal structure of methionyl-tRNAfMet transformylase complexed with the initiator formyl-methionyl-tRNAfMet.
  EMBO J, 17, 6819-6826.
PDB code: 2fmt
9628739 J.H.Shim, and S.J.Benkovic (1998).
Evaluation of the kinetic mechanism of Escherichia coli glycinamide ribonucleotide transformylase.
  Biochemistry, 37, 8776-8782.  
9843398 V.Ramesh, S.Gite, and U.L.RajBhandary (1998).
Functional interaction of an arginine conserved in the sixteen amino acid insertion module of Escherichia coli methionyl-tRNA formyltransferase with determinants for formylation in the initiator tRNA.
  Biochemistry, 37, 15925-15932.  
9843369 W.Wang, T.J.Kappock, J.Stubbe, and S.E.Ealick (1998).
X-ray crystal structure of glycinamide ribonucleotide synthetase from Escherichia coli.
  Biochemistry, 37, 15647-15662.
PDB code: 1gso
9265631 S.P.Sanghani, and R.G.Moran (1997).
Tight binding of folate substrates and inhibitors to recombinant mouse glycinamide ribonucleotide formyltransferase.
  Biochemistry, 36, 10506-10516.  
9391059 V.Ramesh, S.Gite, Y.Li, and U.L.RajBhandary (1997).
Suppressor mutations in Escherichia coli methionyl-tRNA formyltransferase: role of a 16-amino acid insertion module in initiator tRNA recognition.
  Proc Natl Acad Sci U S A, 94, 13524-13529.  
  8887566 E.Schmitt, S.Blanquet, and Y.Mechulam (1996).
Structure of crystalline Escherichia coli methionyl-tRNA(f)Met formyltransferase: comparison with glycinamide ribonucleotide formyltransferase.
  EMBO J, 15, 4749-4758.
PDB code: 1fmt
8877810 L.Liu, M.G.Nair, and R.L.Kisliuk (1996).
Novel nonclassical inhibitors of glycinamide ribonucleotide formyltransferase: 10-formyl and 10-hydroxymethyl derivatives of 5,8,10-trideazapteroic acid.
  J Mol Recognit, 9, 169-174.  
8842143 L.Rey, D.Fernández, B.Brito, Y.Hernando, J.M.Palacios, J.Imperial, and T.Ruiz-Argüeso (1996).
The hydrogenase gene cluster of Rhizobium leguminosarum bv. viciae contains an additional gene (hypX), which encodes a protein with sequence similarity to the N10-formyltetrahydrofolate-dependent enzyme family and is required for nickel-dependent hydrogenase processing and activity.
  Mol Gen Genet, 252, 237-248.  
8688421 M.S.Warren, A.E.Marolewski, and S.J.Benkovic (1996).
A rapid screen of active site mutants in glycinamide ribonucleotide transformylase.
  Biochemistry, 35, 8855-8862.  
8958185 T.J.Boritzki, C.A.Barlett, C.Zhang, and E.F.Howland (1996).
AG2034: a novel inhibitor of glycinamide ribonucleotide formyltransferase.
  Invest New Drugs, 14, 295-303.  
8749362 J.L.Smith (1995).
Enzymes of nucleotide synthesis.
  Curr Opin Struct Biol, 5, 752-757.  
  7868604 P.L.Nagy, A.Marolewski, S.J.Benkovic, and H.Zalkin (1995).
Formyltetrahydrofolate hydrolase, a regulatory enzyme that functions to balance pools of tetrahydrofolate and one-carbon tetrahydrofolate adducts in Escherichia coli.
  J Bacteriol, 177, 1292-1298.  
  8226647 P.L.Nagy, G.M.McCorkle, and H.Zalkin (1993).
purU, a source of formate for purT-dependent phosphoribosyl-N-formylglycinamide synthesis.
  J Bacteriol, 175, 7066-7073.  
  8501063 P.Nygaard, and J.M.Smith (1993).
Evidence for a novel glycinamide ribonucleotide transformylase in Escherichia coli.
  J Bacteriol, 175, 3591-3597.  
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.