Disease relevance of Glycineamideribotide

• Structure of crystalline Escherichia coli methionyl-tRNA(f)Met formyltransferase: comparison with glycinamide ribonucleotide formyltransferase [1].
• In tests against other folate-utilizing enzymes, 11a and 11b were found to be inhibitors of glycinamide ribonucleotide formyltransferase (GAR formyltransferase) from one bacterial (Lactobacillus casei) and two mammalian (Manca and L1210) sources with 11a being decidedly more inhibitory than 11b [2].
• Pemetrexed (Alimta; Eli Lilly and Co, Indianapolis, IN) is a novel antifolate/antimetabolite with activity in breast cancer and has well-defined molecular targets, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase [3].
• The purT gene from Bacillus subtilis encoding the formate-dependent glycinamide ribonucleotide transformylase T was cloned by functional complementation of an Escherichia coli purN purT double mutant [4].

Psychiatry related information on Glycineamideribotide

• Glycinamide ribonucleotide synthetase activity in lymphocytes from patients with Alzheimer's disease and normal controls [5].

High impact information on Glycineamideribotide

• SCRATCHY libraries were created from the glycinamide-ribonucleotide formyltransferase (GART) genes from Escherichia coli (purN) and human (hGART) [6].
• To ascertain whether this strategy pertains to the de novo purine enzymes, the localization pattern of the third purine enzyme, glycinamide ribonucleotide transformylase (GAR Tfase) was monitored in live Escherichia coli and mammalian cells [7].
• The enzymes encoded by the Escherichia coli genes purU and purN, N10-formyltetrahydrofolate hydrolase and glycinamide ribonucleotide (GAR) transformylase, respectively, catalyze similiar yet distinct reactions [8].
• The specific activity of two hybrid proteins was within 100- to 1000-fold of the native purN GAR transformylase validating the approach of constructing an enzyme active site from functional parts of others [8].
• Assignment of a third purine biosynthetic gene (glycinamide ribonucleotide transformylase) to human chromosome 21 [9].

Chemical compound and disease context of Glycineamideribotide

• In the Escherichia coli glycinamide ribonucleotide formyltransferase, which also uses fTHF as the formyl donor, Asn-106, His-108 and Asp-144 participate in the catalytic step [10].

Biological context of Glycineamideribotide

• The results provide evidence indicating that glycinamide ribonucleotide synthetase is syntenic with superoxide dismutase (soluble) and is located on human chromosome 21 [11].
• Synteny between glycinamide ribonucleotide synthetase and superoxide dismutase (soluble) [11].
• Substrate specificity of glycinamide ribonucleotide synthetase from chicken liver [12].
• We concluded that the robust initial response of the p53 pathway to GART inhibitors is not transcriptionally propagated to target genes due to a defect in p53 post-translational modifications and a failure to open chromatin structure despite promoter binding of this unmodified p53 [13].
• Intronic polyadenylation in the human glycinamide ribonucleotide formyltransferase gene [14].

Anatomical context of Glycineamideribotide

• Using a series of human-hamster hybrid cell lines, a gene coding for glycinamide ribonucleotide transformylase was mapped to human chromosome 21 [9].
• Many cultured human cell lines show large synergistic cytotoxicity when an inhibitor of dihydrofolate reductase (EC 1.5.1.3) is combined with an antifolate inhibitor of thymidylate synthase (EC 2. 1.1.45) or with an antifolate inhibitor of glycinamide ribonucleotide formyltransferase (EC 2.1.2.2) [15].
• Glycinamide ribonucleotide (GAR) transformylase from HeLa cells has been purified 200-fold to apparent homogeneity with a procedure using two affinity resins [16].
• Folic acid-enhanced synergy for the combination of trimetrexate plus the glycinamide ribonucleotide formyltransferase inhibitor 4-[2-(2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimidino[5,4,6][1,4]thiazin -6-yl)-(S)-ethyl]-2,5-thienoylamino-L-glutamic acid (AG2034): comparison across sensitive and resistant human tumor cell lines [17].
• Gene dosage effect for glycinamide ribonucleotide synthetase in human fibroblasts trisomic for chromosome 21 [18].

Associations of Glycineamideribotide with other chemical compounds

• Included in this superfamily are d-Ala d-Ala ligase, glutathione synthetase, carbamyl phosphate synthetase, N(5)-carboxyaminoimidazole ribonucleotide synthetase, and glycinamide ribonucleotide transformylase, all of which have known three-dimensional structures and contain a number of highly conserved residues between them [19].
• Conversely, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase decreased after pemetrexed chemotherapy [20].
• Expression of baseline dihydrofolate reductase and glycinamide ribonucleotide formyl transferase tended to be higher in responders but this association was not significant (P > 0.311) [20].
• Side chain modified 5-deazafolate and 5-deazatetrahydrofolate analogues as mammalian folylpolyglutamate synthetase and glycinamide ribonucleotide formyltransferase inhibitors: synthesis and in vitro biological evaluation [21].
• The rate of formation of 5-phosphoribosylamine (PRA) from ribose 5-phosphate and NH3 and its rate of decomposition as a function of pH have been determined with a glycinamide ribonucleotide synthetase trapping system fashioned after earlier studies of Nierlich and Magasanik [Nierlich, D. P., & Magasanik, B. (1965) J. Biol. Chem. 240, 366] [22].

Gene context of Glycineamideribotide

• Each of the cDNAs encode peptides comprising the complete enzymatic domain of either GAR synthetase, GAR transformylase or AIR synthetase [23].
• Pemetrexed is a new-generation antifolate that in its higher polyglutamyl forms is a potent, direct inhibitor of thymidylate synthase and, to a lesser extent, glycinamide ribonucleotide transformylase [24].
• The glycinamide ribonucleotide formyltransferase gene, Gart, is encoded 5' of Son in a head-to-head arrangement, with the start of both genes lying within 899 bp [25].
• The purT gene homolog encoding the glycinamide ribonucleotide transformylase T starts about 200 bp away from this open reading frame in the opposite direction [26].
• In humans, the second, third and fifth steps of de novo purine biosynthesis are catalyzed by a trifunctional protein with glycinamide ribonucleotide synthetase (GARS), aminoimidazole ribonucleotide synthetase (AIRS) and glycinamide ribonucleotide formyltransferase (GART) enzymatic activities [27].

Analytical, diagnostic and therapeutic context of Glycineamideribotide

• We compared the ability of ITCHY and DNA shuffling to create interspecies fusion libraries between fragments of the Escherichia coli and human glycinamide ribonucleotide transformylase genes, which have only 50% identity on the DNA level [28].
• Differentiation of human and hamster glycinamide ribonucleotide transformylase was accomplished via an immunoprecipitation assay that employed a polyclonal antibody raised against the human enzyme [9].
• High performance liquid chromatography analysis revealed that each cell type metabolized greater than or equal to 80% of the internalized drug to polyglutamated forms, which are more potent glycinamide ribonucleotide transformylase inhibitors [29].
• Crystal structure of glycinamide ribonucleotide transformylase from Escherichia coli at 3.0 A resolution. A target enzyme for chemotherapy [30].
• A sensitive and specific radioimmunoassay for LY309887, a potent inhibitor of glycinamide ribonucleotide formyltransferase [31].

References