Crystal structure of glycinamide ribonucleotide transformylase from Escherichia coli at 3.0 A resolution. A target enzyme for chemotherapy. 1992

P Chen, and U Schulze-Gahmen, and E A Stura, and J Inglese, and D L Johnson, and A Marolewski, and S J Benkovic, and I A Wilson
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.

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.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D010710 Phosphates Inorganic salts of phosphoric acid. Inorganic Phosphate,Phosphates, Inorganic,Inorganic Phosphates,Orthophosphate,Phosphate,Phosphate, Inorganic
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D003461 Crystallography The branch of science that deals with the geometric description of crystals and their internal arrangement. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Crystallographies
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D000217 Acyltransferases Enzymes from the transferase class that catalyze the transfer of acyl groups from donor to acceptor, forming either esters or amides. (From Enzyme Nomenclature 1992) EC 2.3. Acyltransferase
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D014961 X-Ray Diffraction The scattering of x-rays by matter, especially crystals, with accompanying variation in intensity due to interference effects. Analysis of the crystal structure of materials is performed by passing x-rays through them and registering the diffraction image of the rays (CRYSTALLOGRAPHY, X-RAY). (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Xray Diffraction,Diffraction, X-Ray,Diffraction, Xray,Diffractions, X-Ray,Diffractions, Xray,X Ray Diffraction,X-Ray Diffractions,Xray Diffractions
D051026 Phosphoribosylglycinamide Formyltransferase An enzyme that catalyzes the transfer of a formyl group from N10-formyltetrahydrofolate to N1-(5-phospho-D-ribosyl)glycinamide to yield N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide and tetrahydrofolate. It plays a role in the de novo purine biosynthetic pathway. 2-Amino-N-Ribosylacetamide 5'-Phosphate Transformylase,5'-Phosphoribosylglycinamide Transformylase,GAR Formyltransferase,GAR Transformylase,GARTFase,Glycinamide Ribonucleotide Transformylase,Glycinamideribotide Transformylase,2 Amino N Ribosylacetamide 5' Phosphate Transformylase,5' Phosphoribosylglycinamide Transformylase,5'-Phosphate Transformylase, 2-Amino-N-Ribosylacetamide,Formyltransferase, GAR,Formyltransferase, Phosphoribosylglycinamide,Ribonucleotide Transformylase, Glycinamide,Transformylase, 2-Amino-N-Ribosylacetamide 5'-Phosphate,Transformylase, 5'-Phosphoribosylglycinamide,Transformylase, GAR,Transformylase, Glycinamide Ribonucleotide,Transformylase, Glycinamideribotide
D019877 Hydroxymethyl and Formyl Transferases Enzymes that catalyze the transfer of hydroxymethyl or formyl groups. EC 2.1.2. Formyl Transferase,Formyltransferase,Hydroxymethyl Transferase,Hydroxymethyl and Formyl Transferase,Hydroxymethyltransferase,Transhydroxymethylase,Formyl Transferases,Formyltransferases,Hydroxymethyl Transferases,Hydroxymethyltransferases,Transformylase,Transformylases,Transhydroxymethylases,Transferase, Formyl,Transferase, Hydroxymethyl,Transferases, Formyl,Transferases, Hydroxymethyl

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