PDBsum entry 1grc

Transferase(formyl)

PDB id: 1grc

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

Protein chains

P08179  (PUR3_ECOLI) -  Phosphoribosylglycinamide formyltransferase from Escherichia coli (strain K12)

Seq: 212 a.a.

Struc: 194 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.2.2 - phosphoribosylglycinamide formyltransferase 1.
• Pathway: Purine Biosynthesis (early stages)
• Reaction: N₁-(5-phospho-beta-D-ribosyl)glycinamide + (6R)-10- formyltetrahydrofolate = N₂-formyl-N₁-(5-phospho-beta-D- ribosyl)glycinamide + (6S)-5,6,7,8-tetrahydrofolate + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added 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.