1GRC

CRYSTAL STRUCTURE OF GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE FROM ESCHERICHIA COLI AT 3.0 ANGSTROMS RESOLUTION: A TARGET ENZYME FOR CHEMOTHERAPY

Summary for 1GRC

• Entry DOI: 10.2210/pdb1grc/pdb
• Descriptor: GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE, PHOSPHATE ION (2 entities in total)
• Functional Keywords: transferase(formyl)
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 46722.45

Authors

Chen, P.,Wilson, I.A. (deposition date: 1992-07-21, release date: 1993-10-31, Last modification date: 2024-02-07)

Primary citation

Chen, P.,Schulze-Gahmen, U.,Stura, E.A.,Inglese, J.,Johnson, D.L.,Marolewski, A.,Benkovic, S.J.,Wilson, I.A.
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, 1992

PubMed 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.

PubMed: 1522592
DOI: 10.1016/0022-2836(92)90698-J

Experimental method

X-RAY DIFFRACTION (3 Å)