Genomes and Genes
formate tetrahydrofolate ligase
Summary: A carbon-nitrogen ligase that catalyzes the formation of 10-formyltetrahydrofolate from formate and tetrahydrofolate in the presence of ATP. In higher eukaryotes the enzyme also contains METHYLENETETRAHYDROFOLATE DEHYDROGENASE (NADP+) and METHENYLTETRAHYDROFOLATE CYCLOHYDROLASE activity.
- Crowley P, Gutierrez J, Hillman J, Bleiweis A. Genetic and physiologic analysis of a formyl-tetrahydrofolate synthetase mutant of Streptococcus mutans. J Bacteriol. 1997;179:1563-72 pubmed..This represents the first characterization of Fhs in Streptococcus...
- Tremblay G, Mejia N, MacKenzie R. The NADP-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase is not expressed in Spodoptera frugiperda cells. J Biol Chem. 1992;267:8281-5 pubmed..Incorporation of labeled glycine and serine into DNA indicates that only serine is a source of one-carbon units. These results suggest that the mitochondria in Sf9 cells do not play a major role in folate-mediated metabolism. ..
- Christensen K, Deng L, Bahous R, Jerome Majewska L, Rozen R. MTHFD1 formyltetrahydrofolate synthetase deficiency, a model for the MTHFD1 R653Q variant, leads to congenital heart defects in mice. Birth Defects Res A Clin Mol Teratol. 2015;103:1031-8 pubmed publisher..Maternal genotype and diet did not have a significant effect on these outcomes. Deficiency of the MTHFD1 10-formyltetrahydrofolate synthetase activity in embryos is associated with increased incidence of congenital heart defects. ..
- Bueno O, Molloy A, Fernandez Ballart J, GarcÃa MinguillÃ¡n C, Ceruelo S, RÃos L, et al. Common Polymorphisms That Affect Folate Transport or Metabolism Modify the Effect of the MTHFR 677C > T Polymorphism on Folate Status. J Nutr. 2016;146:1-8 pubmed publisher..Low folate status risk associated with the MTHFR 677TT genotype varied depending on its combination with other polymorphisms. ..
- Nour J, Rabinowitz J. Isolation and sequencing of the cDNA coding for spinach 10-formyltetrahydrofolate synthetase. Comparisons with the yeast, mammalian, and bacterial proteins. J Biol Chem. 1992;267:16292-6 pubmed..Possible reasons for this are presented. The codon usage and the putative translation initiation sites are examined and compared with other spinach proteins. ..
- Zheng C, Xu J, Shi G, Zhao X, Ren S, Li J, et al. Formate-tetrahydrofolate ligase is involved in the virulence of Streptococcus suis serotype 2. Microb Pathog. 2016;98:149-54 pubmed publisher..suis 2. Our findings provide a new insight into the pathogenesis of S. suis 2. ..
- Tremblay G, MacKenzie R. Primary structure of a folate-dependent trifunctional enzyme from Spodoptera frugiperda. Biochim Biophys Acta. 1995;1261:129-33 pubmed..The cDNA inserted in the yeast expression vector pVT102-U complements a purine auxotrophic yeast strain lacking this enzyme. ..
- Lewinski K, Hui Y, Jakob C, Lovell C, Lebioda L. Crystallization and preliminary crystallographic data for formyltetrahydrofolate synthetase from Clostridium thermoaceticum. J Mol Biol. 1993;229:1153-6 pubmed..A 4.2 A resolution data set has been collected. Analysis of the data using the self-rotation function shows that tetramers have approximate 222 symmetry and are positioned on a crystallographic 2-fold axis. ..
- Ghazouani L, Khalifa S, Abboud N, Perret C, Nicaud V, Ben Khalfallah A, et al. Association of three polymorphisms selected from a genome-wide association study with coronary heart disease in the Tunisian population. J Thromb Thrombolysis. 2010;29:114-8 pubmed publisher..The three SNPs previously reported to be associated with CHD were not replicated in our small sample. ..
- Song S, Vander Velde D, Gunn C, Himes R. Conformation of ATP and ADP bound to N10-formyltetrahydrofolate synthetase determined by TRNOE NMR spectroscopy. Biochemistry. 1994;33:693-8 pubmed..These values are consistent with a nucleotide structure generated by computer modeling after energy minimization, which has X = 90 degrees +/- 6 degrees and psi' = 81 degrees, indicating a high-anti and C3'-endo conformation. ..
- Prasannan P, Pike S, Peng K, Shane B, Appling D. Human mitochondrial C1-tetrahydrofolate synthase: gene structure, tissue distribution of the mRNA, and immunolocalization in Chinese hamster ovary calls. J Biol Chem. 2003;278:43178-43187 pubmed publisher..Yeast cells expressing the full-length human cDNA exhibited elevated 10-formyl-THF synthetase activity, confirming its identification as the human mitochondrial C1-THF synthase. ..
- Nigavekar S, Cannon J. Characterization of genes that are synthetically lethal with ade3 or leu2 in Saccharomyces cerevisiae. Yeast. 2002;19:115-22 pubmed..Therefore, ptr3, bap2 or ssy1 mutants must be leucine prototrophs to grow on rich media. In light of these findings, we propose modifications that should improve the efficiency of synthetic lethal screening procedures. ..
- Matsui H, Kojima N, Tajima K. Diversity of the formyltetrahydrofolate synthetase gene (fhs), a key enzyme for reductive acetogenesis, in the bovine rumen. Biosci Biotechnol Biochem. 2008;72:3273-6 pubmed..Diverse sequences were recovered, the majority of which were clustered with the fhs of authentic acetogens. Low similarity values to known fhs were observed in all sequences, suggesting the presence of unknown acetogens. ..
- Rankin C, Haslam G, Himes R. Sequence and expression of the gene for N10-formyltetrahydrofolate synthetase from Clostridium cylindrosporum. Protein Sci. 1993;2:197-205 pubmed..Certain conserved sequences found in the three clostridial proteins and in the N10-H4folate synthetase portion of eukaryotic C1-H4folate synthases may represent consensus sequences for nucleotide and H4folate binding. ..
- Li R, Moore M, King J. Investigating the regulation of one-carbon metabolism in Arabidopsis thaliana. Plant Cell Physiol. 2003;44:233-41 pubmed
- Stover P, Schirch V. Synthesis of (6S)-5-formyltetrahydropteroyl-polyglutamates and interconversion to other reduced pteroylpolyglutamate derivatives. Anal Biochem. 1992;202:82-8 pubmed..Rapid purification procedures for serine hydroxymethyltransferase and C1-tetrahydrofolate synthase from frozen rabbit livers are presented. ..
- Barbour L, Zhu Y, Xiao W. Improving synthetic lethal screens by regulating the yeast centromere sequence. Genome. 2000;43:910-7 pubmed
- Prabhu V, Chatson K, Abrams G, King J. 13C nuclear magnetic resonance detection of interactions of serine hydroxymethyltransferase with C1-tetrahydrofolate synthase and glycine decarboxylase complex activities in Arabidopsis. Plant Physiol. 1996;112:207-16 pubmed..Nuclear magnetic resonance is a powerful tool for the examination of THF-mediated metabolism in its natural cellular environment. ..
- Suzuki K, Wool I. The primary structure of rat ribosomal protein L23a. The application of homology search to the identification of genes for mammalian and yeast ribosomal proteins and a correlation of rat and yeast ribosomal proteins. J Biol Chem. 1993;268:2755-61 pubmed..In a correlation of rat and yeast ribosomal proteins 48 pairs are shown to be related. ..
- Pike S, Rajendra R, Artzt K, Appling D. Mitochondrial C1-tetrahydrofolate synthase (MTHFD1L) supports the flow of mitochondrial one-carbon units into the methyl cycle in embryos. J Biol Chem. 2010;285:4612-20 pubmed publisher..Thus, a complete pathway of enzymes for supplying 1-C units from the mitochondria to the methyl cycle in embryonic tissues is established. ..
- Marx C, Laukel M, Vorholt J, Lidstrom M. Purification of the formate-tetrahydrofolate ligase from Methylobacterium extorquens AM1 and demonstration of its requirement for methylotrophic growth. J Bacteriol. 2003;185:7169-75 pubmed..extorquens AM1. Rather, our data suggest an alternative model for the role of the H(4)F pathway in this organism in which it functions to convert formate to methylene H(4)F for assimilatory metabolism...
- Song S, Jahansouz H, Himes R. Solvent oxygen is not incorporated into N10-formyltetrahydrofolate in the reaction catalyzed by N10-formyltetrahydrofolate synthetase. FEBS Lett. 1993;332:150-2 pubmed
- Ottesen E, Hong J, Quake S, Leadbetter J. Microfluidic digital PCR enables multigene analysis of individual environmental bacteria. Science. 2006;314:1464-7 pubmed..The ability to systematically identify bacteria carrying a particular gene and to link any two or more genes of interest to single species residing in complex ecosystems opens up new opportunities for research on the environment. ..
- Zhang S, Ruiz Echevarria M, Quan Y, Peltz S. Identification and characterization of a sequence motif involved in nonsense-mediated mRNA decay. Mol Cell Biol. 1995;15:2231-44 pubmed..This sequence motif is one of the few elements that have been identified that can predict regions in genes that can be involved in mRNA turnover. The role of these sequences in mRNA decay is discussed. ..
- Pester M, Brune A. Expression profiles of fhs (FTHFS) genes support the hypothesis that spirochaetes dominate reductive acetogenesis in the hindgut of lower termites. Environ Microbiol. 2006;8:1261-70 pubmed..Our results strongly support the hypothesis that spirochaetes are responsible for reductive acetogenesis in the hindgut of lower, wood-feeding termites. ..
- Christensen K, Hou W, Bahous R, Deng L, Malysheva O, Arning E, et al. Moderate folic acid supplementation and MTHFD1-synthetase deficiency in mice, a model for the R653Q variant, result in embryonic defects and abnormal placental development. Am J Clin Nutr. 2016;104:1459-1469 pubmed..These findings have implications for women with high folate intakes, particularly if they are polymorphic for MTHFD1 R653Q. ..
- Parameswaran P, Zhang H, Torres C, Rittmann B, Krajmalnik Brown R. Microbial community structure in a biofilm anode fed with a fermentable substrate: the significance of hydrogen scavengers. Biotechnol Bioeng. 2010;105:69-78 pubmed publisher..Thus, the community structure in the biofilm anode and suspension reflected the electron-flow distribution and H2-scavenging mechanism. ..
- Kirksey T, Appling D. Site-directed mutagenesis of a highly conserved aspartate in the putative 10-formyl-tetrahydrofolate binding site of yeast C1-tetrahydrofolate synthase. Arch Biochem Biophys. 1996;333:251-9 pubmed..Thus, these results suggest that the 10-formyl-THF binding site differs significantly between the GAR transformylase and 10-formyl-THF synthetase families, and that the conserved aspartate plays different roles in the two enzymes. ..
- Pizzorno G, Moroson B, Cashmore A, Russello O, Mayer J, Galivan J, et al. Multifactorial resistance to 5,10-dideazatetrahydrofolic acid in cell lines derived from human lymphoblastic leukemia CCRF-CEM. Cancer Res. 1995;55:566-73 pubmed..Cross-resistance was also shown toward other deazafolate analogues for both short- and long-term exposures. ..
- Rozen R, Barton D, Du J, Hum D, MacKenzie R, Francke U. Chromosomal localization of the gene for the human trifunctional enzyme, methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase. Am J Hum Genet. 1989;44:781-6 pubmed..A second hybridizing sequence, possibly a pseudogene, was identified near the centromere of the X chromosome, at Xp11. ..
- Christensen K, Rohlicek C, Andelfinger G, Michaud J, Bigras J, Richter A, et al. The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. Hum Mutat. 2009;30:212-20 pubmed publisher..Further evaluation of this polymorphism in folate)related disorders and its potential interaction with folate status is warranted. ..
- Leaphart A, Friez M, Lovell C. Formyltetrahydrofolate synthetase sequences from salt marsh plant roots reveal a diversity of acetogenic bacteria and other bacterial functional groups. Appl Environ Microbiol. 2003;69:693-6 pubmed..Most other FTHFS or FTHFS-like sequences grouped with those from sulfate-reducing bacteria. Several sequences that grouped with Sphingomonas paucimobilis ligH were also recovered. ..
- Ganz A, Shields K, Fomin V, Lopez Y, Mohan S, Lovesky J, et al. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis. FASEB J. 2016;30:3321-3333 pubmed..C., Stover, J. A., Vitiello, G. A., Malysheva, O. V., Mudrak, E., Caudill, M. A. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis. ..
- Hum D, Bell A, Rozen R, MacKenzie R. Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase. J Biol Chem. 1988;263:15946-50 pubmed..A region was identified which probably serves as a link between these two major domains of the human enzyme. The synthetase domain contains two regions that are homologous to consensus sequences for an ATP-binding site. ..
- Whitehead T, Park M, Rabinowitz J. Distribution of 10-formyltetrahydrofolate synthetase in eubacteria. J Bacteriol. 1988;170:995-7 pubmed..Organisms from several genera were found to lack detectable synthetase activity; however, all organisms tested were found to contain 5,10-methylenetetrahydrofolate dehydrogenase activity. ..
- Smithers G, Jahansouz H, Kofron J, Himes R, Reed G. Substrate activity of synthetic formyl phosphate in the reaction catalyzed by formyltetrahydrofolate synthetase. Biochemistry. 1987;26:3943-8 pubmed..Kinetic analysis of the formyl phosphate supported reactions indicates that the low steady-state rates observed for the synthetic intermediate are most likely due to the sequential nature of the normal reaction. ..
- Tzortzatou Stathopoulou F, Mikraki V, Xaidara A, Moschovi M, Evangelinos V, Panagopoulos K. Activity of 5-formyl tetrahydrofolate cyclodehydrase and 5,10-methenyl tetrahydrofolate cyclohydrolase in primary brain tumors in children. Pediatr Hematol Oncol. 1996;13:511-9 pubmed..A clear understanding of the mode of action of these enzymes may contribute to devising novel therapeutic strategies. ..
- Deacon R, Perry J, Lumb M, Chanarin I. Cobalamin inactivation induces formyltetrahydrofolate synthetase. FEBS Lett. 1990;263:303-4 pubmed..There are contradictory reports on the effect of cobalamin inactivation on CHO-H4PteGlu synthetase. This study confirms a significant increase in synthetase activity following cobalamin inactivation. ..
- Strong W, Tendler S, Seither R, Goldman I, Schirch V. Purification and properties of serine hydroxymethyltransferase and C1-tetrahydrofolate synthase from L1210 cells. J Biol Chem. 1990;265:12149-55 pubmed
- Shih C, Chen V, Gossett L, Gates S, MacKellar W, Habeck L, et al. LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res. 1997;57:1116-23 pubmed..Therefore, our data suggest that LY231514 is a novel classical antifolate, the antitumor activity of which may result from simultaneous and multiple inhibition of several key folate-requiring enzymes via its polyglutamated metabolites. ..
- Lovell C, Przybyla A, Ljungdahl L. Cloning and expression in Escherichia coli of the Clostridium thermoaceticum gene encoding thermostable formyltetrahydrofolate synthetase. Arch Microbiol. 1988;149:280-5 pubmed..FTHFS was purified to homogeneity from CRL47. The purified enzyme behaved during electrophoresis and gel chromatography and it had similar specific activity and thermostability as the enzyme purified from C. thermoaceticum. ..
- Parle McDermott A, Pangilinan F, Mills J, Signore C, Molloy A, Cotter A, et al. A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss. Mol Hum Reprod. 2005;11:477-80 pubmed..Neither showed evidence of significantly affecting the maternal risk of having a second trimester pregnancy loss. In conclusion, the MTHFD1 1958AA genotype may be an important maternal risk factor to consider during pregnancy...
- Goyer A, Collakova E, Diaz De La Garza R, Quinlivan E, Williamson J, Gregory J, et al. 5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Arabidopsis leaves. J Biol Chem. 2005;280:26137-42 pubmed..However, the near-normal growth of the mutant shows that even exceptionally high 5-CHO-THF levels do not much affect fluxes through SHMT or any other folate-dependent reaction, i.e. that 5-CHO-THF is well tolerated in plants. ..
- Patel H, Christensen K, Mejia N, MacKenzie R. Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase derived from a trifunctional methylenetetrahydrofolate dehydrogenase-cyclohydrolase-synthetase. Arch Biochem Biophys. 2002;403:145-8 pubmed..The mt-DC should be considered in models of one-carbon folate fluxes in mammals. ..
- Brody L, Conley M, Cox C, Kirke P, McKeever M, Mills J, et al. A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defect. Am J Hum Genet. 2002;71:1207-15 pubmed..003). We conclude that genetic variation in the MTHFD1 gene is associated with an increase in the genetically determined risk that a woman will bear a child with NTD and that the gene may be associated with decreased embryo survival. ..
- Song J, Rabinowitz J. The N-terminal, dehydrogenase/cyclohydrolase domain of yeast cytoplasmic trifunctional C1-tetrahydrofolate synthase requires the C-terminal, synthetase domain for the catalytic activity in vitro. FEBS Lett. 1995;376:229-32 pubmed..These results indicate that the N-terminal D/C domain of C1-THF synthase requires the C-terminal 10-formyl-THF synthetase domain for stable catalytic activity in vitro. ..
- Pawelek P, MacKenzie R. Methenyltetrahydrofolate cyclohydrolase is rate limiting for the enzymatic conversion of 10-formyltetrahydrofolate to 5,10-methylenetetrahydrofolate in bifunctional dehydrogenase-cyclohydrolase enzymes. Biochemistry. 1998;37:1109-15 pubmed..These results imply that essentially all of the methenylH4folate produced by the cyclohydrolase in the reverse reaction is channeled to the dehydrogenase. ..
- Minami M, Inagaki H, Katsumata M, Miyake K, Tomoda A. Inhibitory action of chloramine on formate-metabolizing system. Studies suggested by an unusual case record. Biochem Pharmacol. 1993;45:1059-64 pubmed..The inhibition of the enzyme by chloramine (2.7-100.8 microM) was confirmed by in vitro experiments, using the purified enzyme, formaldehyde dehydrogenase. ..
- McNeil J, Bognar A, Pearlman R. In vivo analysis of folate coenzymes and their compartmentation in Saccharomyces cerevisiae. Genetics. 1996;142:371-81 pubmed..Inactivation of SHM1, SHM2 and ADE3 is required to render yeast auxotrophic for TMP and methionine, suggesting that TMP synthesized in mitochondria may be available to the cytoplasmic compartment. ..
- Whitehead T, Rabinowitz J. Nucleotide sequence of the Clostridium acidiurici ("Clostridium acidi-urici") gene for 10-formyltetrahydrofolate synthetase shows extensive amino acid homology with the trifunctional enzyme C1-tetrahydrofolate synthase from Saccharomyces ce. J Bacteriol. 1988;170:3255-61 pubmed..A comparison of the amino acid sequences of the monofunctional synthetase and the eucaryotic trifunctional enzyme, C1-tetrahydrofolate synthase, from Saccharomyces cerevisiae demonstrated a region of strong homology. ..
- Lovell C, Leaphart A. Community-level analysis: key genes of CO2-reductive acetogenesis. Methods Enzymol. 2005;397:454-69 pubmed..Information on the types of sequences that have been recovered from natural acetogen habitats and how they have been interpreted is also included. ..