Structures of Apo and Complexed Escherichia coli Glycinamide Ribonucleotide Transformylase

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-07, Vol.89 (13), p.6114-6118
• Main Authors: Almassy, Robert J., Janson, Cheryl A., Kan, Chen-Chen, Hostomska, Zuzana
• Format: Article
• Language: English
• Subjects: Active sites; Acyltransferases - antagonists & inhibitors; Acyltransferases - metabolism; Acyltransferases - ultrastructure; Analytical, structural and metabolic biochemistry; Apoproteins - ultrastructure; Atoms; Bacteria; Binding Sites; Biochemistry; Biological and medical sciences; Cancer; Computer Graphics; Crystal structure; Crystallography; Crystals; Design; Drugs; Enzymes; Enzymes and enzyme inhibitors; Escherichia coli; Escherichia coli - enzymology; Fundamental and applied biological sciences. Psychology; Hydrogen Bonding; Hydroxymethyl and Formyl Transferases; Medical research; Models, Molecular; Molecules; Phosphates; Phosphoribosylglycinamide Formyltransferase; Protein Conformation; Proteins; Recombinant Proteins; Ribonucleotides; Therapy; Transferases; X-Ray Diffraction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.13.6114

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-Å resolution and as a ternary complex with the substrate glycinamide ribonucleotide and a folate inhibitor at 2.5-Å resolution. The structure is a modified doubly wound α/β 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.