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PDBsum entry 1grc

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protein ligands Protein-protein interface(s) links
Transferase(formyl) PDB id
1grc
Jmol
Contents
Protein chains
194 a.a. *
Ligands
PO4 ×2
* Residue conservation analysis
PDB id:
1grc
Name: Transferase(formyl)
Title: Crystal structure of glycinamide ribonucleotide transformylase from escherichia coli at 3.0 angstroms resolution: a target enzyme for chemotherapy
Structure: Glycinamide ribonucleotide transformylase. Chain: a, b. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562.
Resolution:
3.00Å     R-factor:   0.190    
Authors: P.Chen,I.A.Wilson
Key ref:
P.Chen et al. (1992). Crystal structure of glycinamide ribonucleotide transformylase from Escherichia coli at 3.0 A resolution. A target enzyme for chemotherapy. J Mol Biol, 227, 283-292. PubMed id: 1522592 DOI: 10.1016/0022-2836(92)90698-J
Date:
21-Jul-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.
194 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
= tetrahydrofolate
+ 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   5 terms 
  Biochemical function     transferase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/0022-2836(92)90698-J J Mol Biol 227:283-292 (1992)
PubMed id: 1522592  
 
 
Crystal structure of glycinamide ribonucleotide transformylase from Escherichia coli at 3.0 A resolution. A target enzyme for chemotherapy.
P.Chen, U.Schulze-Gahmen, E.A.Stura, J.Inglese, D.L.Johnson, A.Marolewski, S.J.Benkovic, I.A.Wilson.
 
  ABSTRACT  
 
The atomic structure of glycinamide ribonucleotide transformylase, an essential enzyme in purine biosynthesis, has been determined at 3.0 A resolution. The last three C-terminal residues and a sequence stretch of 18 residues (residues 113 to 130) are not visible in the electron density map. The enzyme forms a dimer in the crystal structure. Each monomer is divided into two domains, which are connected by a central mainly parallel seven-stranded beta-sheet. The N-terminal domain contains a Rossmann type mononucleotide fold with a phosphate ion bound to the C-terminal end of the first beta-strand. A long narrow cleft stretches from the phosphate to a conserved aspartic acid, Asp144, which has been suggested as an active-site residue. The cleft is lined by a cluster of residues, which are conserved between bacterial, yeast, avian and human enzymes, and likely represents the binding pocket and active site of the enzyme. GAR Tfase binds a reduced folate cofactor and glycinamide ribonucleotide for the catalysis of one of the initial steps in purine biosynthesis. Folate analogs and multi-substrate inhibitors of the enzyme have antineoplastic effects and the structure determination of the unliganded enzyme and enzyme-inhibitor complexes will aid the development of anti-cancer drugs.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. (a). Stereo view of the F,-Fc electron density omit map. (Bhat & Cohen, 1984; Rini et nl., 1992) for the phosphate binding loop of GAR Tfase in molecule 1. The map is contoured at 2.5 u. The bckbone of residues Am10 to Asnl3 and the ide-chain amide of Asnl3 are in hydrogen bonding distance to the phosphate ion. (b) Stereo' view of the Fo-Fc electron density omit map around the putative active ite esidue Asp144 in molecule 1. The omit map is contoured at 2.5 rs. The side-chain of Asp144 is hydrogen bonded to the conserved residues His108 and HisI37.
Figure 4.
Figure 4. Stereo view of a C'' trace of the GAR Tfase with only those side-chans displayed that are conserved in all known sequences (Aimi et al.; I990). The conserved esidues coored in yellow line a narrow cleft between the 2 domains f the enzyme. The cleft stretches from the bound phosphate ion (red) to Asp144 and is probably the binding pocket and active site of the enzyme. The other conserved residues are shown in green. None of these conserved residues are located in the dimer interface. The Figure was calculated with the program MCS (Connolly, 1985).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 227, 283-292) copyright 1992.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18845790 F.E.Boccalatte, C.Voena, C.Riganti, A.Bosia, L.D'Amico, L.Riera, M.Cheng, B.Ruggeri, O.N.Jensen, V.L.Goss, K.Lee, J.Nardone, J.Rush, R.D.Polakiewicz, M.J.Comb, R.Chiarle, and G.Inghirami (2009).
The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL.
  Blood, 113, 2776-2790.  
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.  
14729668 A.A.Chumanevich, S.A.Krupenko, and C.Davies (2004).
The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase domain.
  J Biol Chem, 279, 14355-14364.
PDB code: 1s3i
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.  
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.  
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.  
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
10584075 S.Roy (1999).
Multifunctional enzymes and evolution of biosynthetic pathways: retro-evolution by jumps.
  Proteins, 37, 303-309.  
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.  
9354240 D.L.Boger, N.E.Haynes, M.S.Warren, J.Ramcharan, A.E.Marolewski, P.A.Kitos, and S.J.Benkovic (1997).
Abenzyl 10-formyl-trideazafolic acid (abenzyl 10-formyl-TDAF): an effective inhibitor of glycinamide ribonucleotide transformylase.
  Bioorg Med Chem, 5, 1847-1852.  
  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
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.  
8749362 J.L.Smith (1995).
Enzymes of nucleotide synthesis.
  Curr Opin Struct Biol, 5, 752-757.  
  7849601 W.R.Taylor, T.P.Flores, and C.A.Orengo (1994).
Multiple protein structure alignment.
  Protein Sci, 3, 1858-1870.  
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.