hydroxymethyl and formyl transferases


Summary: Enzymes that catalyze the transfer of hydroxymethyl or formyl groups. EC 2.1.2.

Top Publications

  1. Li Y, Holmes W, Appling D, RajBhandary U. Initiation of protein synthesis in Saccharomyces cerevisiae mitochondria without formylation of the initiator tRNA. J Bacteriol. 2000;182:2886-92 pubmed
    ..The only growth phenotype observed was a longer lag time during growth on nonfermentable carbon sources in minimal media for the mis1 deletion strain but not for the fmt1 deletion strain. ..
  2. Dervieux T, Furst D, Lein D, Capps R, Smith K, Walsh M, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004;50:2766-74 pubmed
    ..01). These data suggest that measuring RBC MTXPG levels and/or the common polymorphisms in the folate-purine-pyrimidine pathway may help in monitoring MTX therapy. ..
  3. Weisman M, Furst D, Park G, Kremer J, Smith K, Wallace D, et al. Risk genotypes in folate-dependent enzymes and their association with methotrexate-related side effects in rheumatoid arthritis. Arthritis Rheum. 2006;54:607-12 pubmed
    ..01). These data suggest that a composite index of the cumulative risk genotypes in folate-dependent enzymes may be an effective means of profiling RA patients who develop side effects to MTX. ..
  4. Campalani E, Arenas M, Marinaki A, Lewis C, Barker J, Smith C. Polymorphisms in folate, pyrimidine, and purine metabolism are associated with efficacy and toxicity of methotrexate in psoriasis. J Invest Dermatol. 2007;127:1860-7 pubmed
    ..We have demonstrated preliminary evidence that specific polymorphisms of enzymes involved in folate, pyrimidine, and purine metabolism could be useful in predicting clinical response to methotrexate in patients with psoriasis. ..
  5. Lee Y, Cui J, Costenbader K, Shadick N, Weinblatt M, Karlson E. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Rheumatology (Oxford). 2009;48:613-7 pubmed publisher
    ..Further studies are needed to clarify the relationship between ATIC polymorphisms, disease activity and treatment response. ..
  6. Newton D, Creuzenet C, Mangroo D. Formylation is not essential for initiation of protein synthesis in all eubacteria. J Biol Chem. 1999;274:22143-6 pubmed
    ..Therefore, the dogma that eubacteria require formylation of the initiator methionyl-tRNA for initiation of protein synthesis may have been an invalid generalization of results obtained with E. coli. ..
  7. Guillon J, Mechulam Y, Schmitter J, Blanquet S, Fayat G. Disruption of the gene for Met-tRNA(fMet) formyltransferase severely impairs growth of Escherichia coli. J Bacteriol. 1992;174:4294-301 pubmed
    ..At 37 degrees C, in a rich medium, the absence of a functional fmt gene reduced the growth rate to 0.28 doubling per h, from 2.3 for the control strain. At 42 degrees C, the studied fmt mutant strain did not grow further. ..
  8. Wallis N, Dardel F, Blanquet S. Heteronuclear NMR studies of the interactions of 15N-labeled methionine-specific transfer RNAs with methionyl-tRNA transformylase. Biochemistry. 1995;34:7668-77 pubmed
    ..The loss of intensity of the acceptor stem resonances suggests that this part of tRNAfMet melts upon binding to the enzyme. ..
  9. Richter S, Messer W. Genetic structure of the dnaA region of the cyanobacterium Synechocystis sp. strain PCC6803. J Bacteriol. 1995;177:4245-51 pubmed
    ..Downstream of the dnaA gene we detected the start of the psbDC operon, which codes for the photosystem II reaction center proteins D2 and CP43 that are involved in the positioning of chlorophyll a. ..

More Information


  1. Schw rer B, Breitung J, Klein A, Stetter K, Thauer R. Formylmethanofuran: tetrahydromethanopterin formyltransferase and N5,N10-methylenetetrahydromethanopterin dehydrogenase from the sulfate-reducing Archaeoglobus fulgidus: similarities with the enzymes from methanogenic Archaea. Arch Microbiol. 1993;159:225-32 pubmed
    ..A comparison of the N-terminal amino acid sequences and of other molecular properties with those of the respective enzymes from three methanogenic Archaea revealed a high degree of similarity...
  2. Vivekananda J, Beck C, Oliver D. Monoclonal antibodies as tools in membrane biochemistry. Identification and partial characterization of the dicarboxylate transporter from pea leaf mitochondria. J Biol Chem. 1988;263:4782-8 pubmed
    ..The techniques described should prove useful for identifying a number of membrane proteins that can be assayed in situ but are difficult to assay following dissolution of the membrane. ..
  3. Vaughan M, Sampson P, Honek J. Methionine in and out of proteins: targets for drug design. Curr Med Chem. 2002;9:385-409 pubmed
    ..This review critically analyzes the future potential for inhibition of enzymes in this pathway, allowing for a pragmatic view of the success of inhibitor developments and highlighting areas in which further investigations are warranted. ..
  4. Bosello M, Mielcarek A, Giessen T, Marahiel M. An enzymatic pathway for the biosynthesis of the formylhydroxyornithine required for rhodochelin iron coordination. Biochemistry. 2012;51:3059-66 pubmed publisher
    ..2004) Arch. Microbiol.182, 313-325; Pohlmann, V. (2008) Org. Biomol. Chem.6, 1843-1848]. ..
  5. Lewandowski T, Huang J, Fan F, Rogers S, Gentry D, Holland R, et al. Staphylococcus aureus formyl-methionyl transferase mutants demonstrate reduced virulence factor production and pathogenicity. Antimicrob Agents Chemother. 2013;57:2929-36 pubmed publisher
  6. Saraf M, Maranas C. Using a residue clash map to functionally characterize protein recombination hybrids. Protein Eng. 2003;16:1025-34 pubmed
    ..This suggests that residue clash maps can provide quantitative guidelines for the placement of crossovers in the design of protein recombination experiments. ..
  7. Bronder J, Moran R. A defect in the p53 response pathway induced by de novo purine synthesis inhibition. J Biol Chem. 2003;278:48861-71 pubmed
  8. Vallée M, Guay F, Beaudry D, Matte J, Blouin R, Laforest J, et al. Effects of breed, parity, and folic Acid supplement on the expression of folate metabolism genes in endometrial and embryonic tissues from sows in early pregnancy. Biol Reprod. 2002;67:1259-67 pubmed
  9. Gooljarsingh L, Ramcharan J, Gilroy S, Benkovic S. Localization of GAR transformylase in Escherichia coli and mammalian cells. Proc Natl Acad Sci U S A. 2001;98:6565-70 pubmed
    ..Thus, GAR Tfase is not localized to an existing cellular architecture, so this device is probably not used to concentrate the members of the pathway. However, discrete clusters of the pathway may still exist throughout the cytoplasm. ..
  10. Toone J, Applegarth D, Coulter Mackie M, James E. Recurrent mutations in P- and T-proteins of the glycine cleavage complex and a novel T-protein mutation (N145I): a strategy for the molecular investigation of patients with nonketotic hyperglycinemia (NKH). Mol Genet Metab. 2001;72:322-5 pubmed
    ..In addition, a novel point mutation in T-protein, N145I, was found in a single case and a PCR/restriction enzyme assay was developed for its detection. ..
  11. Peña J, Lotze T, Yang Y, Umaña L, Walkiewicz M, Hunter J, et al. Methionyl-tRNA Formyltransferase (MTFMT) Deficiency Mimicking Acquired Demyelinating Disease. J Child Neurol. 2016;31:215-9 pubmed publisher
    ..626C>T mutation in the MTFMT gene. These findings expand the clinical features and neuroimaging spectrum associated with MTFMT mutations to include a relapsing-remitting phenotype. ..
  12. Brodsky G, Barnes T, Bleskan J, Becker L, Cox M, Patterson D. The human GARS-AIRS-GART gene encodes two proteins which are differentially expressed during human brain development and temporally overexpressed in cerebellum of individuals with Down syndrome. Hum Mol Genet. 1997;6:2043-50 pubmed
    ..In contrast, the GARS and GARS-AIRS-GART proteins continue to be expressed during the postnatal development of the cerebellum in individuals with Down syndrome. ..
  13. Beardsley G, Rayl E, Gunn K, Moroson B, Seow H, Anderson K, et al. Structure and functional relationships in human pur H. Adv Exp Med Biol. 1998;431:221-6 pubmed
    ..Among these, we have thus far completed studies on two, Lysine 265 and Histidine 266. These appear to be critically involved in the AICARFT reaction, although whether their role(s) are in catalysis or binding remains to be determined. ..
  14. Sahm H, Eggeling L. D-Pantothenate synthesis in Corynebacterium glutamicum and use of panBC and genes encoding L-valine synthesis for D-pantothenate overproduction. Appl Environ Microbiol. 1999;65:1973-9 pubmed
  15. Orun O, Koch M, Kan B, Svergun D, Petoukhov M, Sayers Z. Structural characterization of T-protein of the Escherichia coli glycine cleavage system by X-ray small angle scattering. Cell Mol Biol (Noisy-le-grand). 2003;49 Online Pub:OL453-9 pubmed
    ..A low resolution model of the protein was constructed ab initio and tentative models of the tertiary structure were built using prediction methods constrained by the scattering data. ..
  16. Sugantino M, Zheng R, Yu M, Blanchard J. Mycobacterium tuberculosis ketopantoate hydroxymethyltransferase: tetrahydrofolate-independent hydroxymethyltransferase and enolization reactions with alpha-keto acids. Biochemistry. 2003;42:191-9 pubmed
    ..These results are discussed in the context of steric restrictions present in the enzyme active site and the stereochemistry of base-catalyzed isotope exchange. ..
  17. Sanghani S, Moran R. Tight binding of folate substrates and inhibitors to recombinant mouse glycinamide ribonucleotide formyltransferase. Biochemistry. 1997;36:10506-16 pubmed
  18. Chakauya E, Coxon K, Wei M, Macdonald M, Barsby T, Abell C, et al. Towards engineering increased pantothenate (vitamin B(5)) levels in plants. Plant Mol Biol. 2008;68:493-503 pubmed publisher
    ..5-2.5 fold increase compared to the wild type plant. Seeds contained the highest vitamin content, indicating that they might be the ideal target for production purposes. ..
  19. Warren R, Smith R, Campalani E, Eyre S, Smith C, Barker J, et al. Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. Br J Dermatol. 2009;160:438-41 pubmed publisher
    ..Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis. ..
  20. Takeuchi N, Vial L, Panvert M, Schmitt E, Watanabe K, Mechulam Y, et al. Recognition of tRNAs by Methionyl-tRNA transformylase from mammalian mitochondria. J Biol Chem. 2001;276:20064-8 pubmed
    ..Moreover, the relatively small importance of the tRNA acceptor stem in the recognition process accounts for the protection against formylation of the mitochondrial tRNAs that share with tRNA(Met) an A(1)U(72) motif. ..
  21. Cheng H, Chong Y, Hwang I, Tavassoli A, Zhang Y, Wilson I, et al. Design, synthesis, and biological evaluation of 10-methanesulfonyl-DDACTHF, 10-methanesulfonyl-5-DACTHF, and 10-methylthio-DDACTHF as potent inhibitors of GAR Tfase and the de novo purine biosynthetic pathway. Bioorg Med Chem. 2005;13:3577-85 pubmed
    ..0 microM and 2, IC50 = 2.0 microM). ..
  22. Lee C, Tibbetts A, Kramer G, Appling D. Yeast AEP3p is an accessory factor in initiation of mitochondrial translation. J Biol Chem. 2009;284:34116-25 pubmed publisher
    ..We propose that Aep3p functions as an accessory initiation factor in mitochondrial protein synthesis. ..
  23. Marolewski A, Smith J, Benkovic S. Cloning and characterization of a new purine biosynthetic enzyme: a non-folate glycinamide ribonucleotide transformylase from E. coli. Biochemistry. 1994;33:2531-7 pubmed
    ..The purT GAR transformylase is the first unknown de novo purine biosynthetic enzyme to be discovered in the last 30 years and represents another step forward in understanding cellular control of purine levels. ..
  24. Wessels J, van der Kooij S, le Cessie S, Kievit W, Barerra P, Allaart C, et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis. Arthritis Rheum. 2007;56:1765-75 pubmed
    ..This study established a model for predicting the efficacy of MTX in patients with RA. This pharmacogenetic model may lead to better-tailored initial treatment decisions in patients with RA. ..
  25. Shima S, Thauer R, Ermler U, Durchschlag H, Tziatzios C, Schubert D. A mutation affecting the association equilibrium of formyltransferase from the hyperthermophilic Methanopyrus kandleri and its influence on the enzyme's activity and thermostability. Eur J Biochem. 2000;267:6619-23 pubmed
    ..With the mutant protein it was shown that tetramerization is not required for activity but is necessary for high thermostability. ..
  26. Shim J, Wall M, Benkovic S, Diaz N, Suarez D, Merz K. Evaluation of the catalytic mechanism of AICAR transformylase by pH-dependent kinetics, mutagenesis, and quantum chemical calculations. J Am Chem Soc. 2001;123:4687-96 pubmed
    ..We propose that His267 interacts with Lys266 to aid in the precise positioning of the general acid catalyst to the N3 of the imidazole of AICAR. ..
  27. Burkin D, Broad T, Lambeth M, Burkin H, Jones C. New gene assignments using a complete, characterized sheep-hamster somatic cell hybrid panel. Anim Genet. 1998;29:48-54 pubmed
    ..Furthermore, the chromosomal assignment of 110 microsatellites was confirmed using this cell panel. ..
  28. Wolan D, Greasley S, Beardsley G, Wilson I. Structural insights into the avian AICAR transformylase mechanism. Biochemistry. 2002;41:15505-13 pubmed
    ..Lys(267) is likely to be involved in the stabilization of the anionic formyl transfer transition state and in subsequent protonation of the THF leaving group. ..
  29. Stauffer L, Stauffer G. Roles for GcvA-binding sites 3 and 2 and the Lrp-binding region in gcvT::lacZ expression in Escherichia coli. Microbiology. 1998;144 ( Pt 10):2865-72 pubmed
    ..Based on these results, a model for gcv regulation is presented in which Lrp plays a primarily structural role, by bending the DNA and GcvA functions as the activator protein. ..
  30. Hilton J, Christensen K, Watkins D, Raby B, Renaud Y, de la Luna S, et al. The molecular basis of glutamate formiminotransferase deficiency. Hum Mutat. 2003;22:67-73 pubmed
    ..These mutations are the first identified in glutamate formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease. ..
  31. Takeuchi N, Kawakami M, Omori A, Ueda T, Spremulli L, Watanabe K. Mammalian mitochondrial methionyl-tRNA transformylase from bovine liver. Purification, characterization, and gene structure. J Biol Chem. 1998;273:15085-90 pubmed
    ..coli MTF which clearly discriminates between the bacterial initiator and elongator Met-tRNAs. These observations are discussed in terms of the presence of a single tRNAMet gene in mammalian mitochondria. ..
  32. Wolan D, Cheong C, Greasley S, Wilson I. Structural insights into the human and avian IMP cyclohydrolase mechanism via crystal structures with the bound XMP inhibitor. Biochemistry. 2004;43:1171-83 pubmed
    ..Several other residues, including Lys66, Tyr104, Asp125, and Lys137', provide substrate specificity and likely enhance the catalytic rate through contributions to acid-base catalysis. ..
  33. Gatzeva Topalova P, May A, Sousa M. Structure and mechanism of ArnA: conformational change implies ordered dehydrogenase mechanism in key enzyme for polymyxin resistance. Structure. 2005;13:929-42 pubmed
    ..The proposed mechanism for ArnA_DH has important implications for the design of selective inhibitors. ..
  34. Kouzuma A, Meng X, Kimura N, Hashimoto K, Watanabe K. Disruption of the putative cell surface polysaccharide biosynthesis gene SO3177 in Shewanella oneidensis MR-1 enhances adhesion to electrodes and current generation in microbial fuel cells. Appl Environ Microbiol. 2010;76:4151-7 pubmed publisher
    ..These results demonstrate that cell surface polysaccharides affect not only the cell adhesion to graphite anodes but also the current generation in MFCs...
  35. Park J, Kim A, Kang Y, Jung Y, Kim H, Kim K. Deacetylation and methylation at histone H3 lysine 9 (H3K9) coordinate chromosome condensation during cell cycle progression. Mol Cells. 2011;31:343-9 pubmed publisher
    ..Collectively, the results of this study indicate that sequential modifications at H3K9 are associated with correct chromosome condensation, and that H3K9me3 may be relevant to the condensation of chromosome length. ..
  36. Guillon J, Meinnel T, Mechulam Y, Lazennec C, Blanquet S, Fayat G. Nucleotides of tRNA governing the specificity of Escherichia coli methionyl-tRNA(fMet) formyltransferase. J Mol Biol. 1992;224:359-67 pubmed
    ..This pattern appears to account fully for the specificity of the formylase and the lack of formylation of any aminoacylated tRNA, excepting the methionyl-tRNA(fMet). ..
  37. Thoden J, Firestine S, Nixon A, Benkovic S, Holden H. Molecular structure of Escherichia coli PurT-encoded glycinamide ribonucleotide transformylase. Biochemistry. 2000;39:8791-802 pubmed
    ..Strikingly, the amino group of GAR that is formylated during the reaction lies at 2.8 A from one of the gamma-phosphoryl oxygens of the AMPPNP. ..
  38. Okamura Ikeda K, Fujiwara K, Motokawa Y. The amino-terminal region of the Escherichia coli T-protein of the glycine cleavage system is essential for proper association with H-protein. Eur J Biochem. 1999;264:446-53 pubmed
    ..These results suggest that EH, when it interacts with ET, causes a change in conformation of ET and that the N-terminal region of ET is essential for the conformational change leading to the proper interaction with EH. ..
  39. Gite S, Li Y, Ramesh V, RajBhandary U. Escherichia coli methionyl-tRNA formyltransferase: role of amino acids conserved in the linker region and in the C-terminal domain on the specific recognition of the initiator tRNA. Biochemistry. 2000;39:2218-26 pubmed
  40. Roberts J, Shibata S, Spicer D, McLeod H, Tombes M, Kyle B, et al. Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks. Cancer Chemother Pharmacol. 2000;45:423-7 pubmed
    ..Both pharmacokinetic and pharmacodynamic factors may contribute to the modest cumulative toxicity observed with AG2034. ..
  41. Merkel W, Nichols B. Characterization and sequence of the Escherichia coli panBCD gene cluster. FEMS Microbiol Lett. 1996;143:247-52 pubmed
    ..Orf3 contained extensive similarity to reading frames defined by E. coli yjiP, yjiQ, yhgA, and yafD. The function of these amino acid sequences is as yet undefined. ..
  42. Chen V, Bewley J, Andis S, Schultz R, Iversen P, Shih C, et al. Preclinical cellular pharmacology of LY231514 (MTA): a comparison with methotrexate, LY309887 and raltitrexed for their effects on intracellular folate and nucleoside triphosphate pools in CCRF-CEM cells. Br J Cancer. 1998;78 Suppl 3:27-34 pubmed
  43. Boger D, Labroli M, Marsilje T, Jin Q, Hedrick M, Baker S, et al. Conformationally restricted analogues designed for selective inhibition of GAR Tfase versus thymidylate synthase or dihydrofolate reductase. Bioorg Med Chem. 2000;8:1075-86 pubmed
  44. Uemura T, Higashi K, Takigawa M, Toida T, Kashiwagi K, Igarashi K. Polyamine modulon in yeast-Stimulation of COX4 synthesis by spermidine at the level of translation. Int J Biochem Cell Biol. 2009;41:2538-45 pubmed publisher
  45. Takatori R, Takahashi K, Tokunaga D, Hojo T, Fujioka M, Asano T, et al. ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients. Clin Exp Rheumatol. 2006;24:546-54 pubmed
    ..These results suggested that the genetic diagnosis of ABCB1 C3435T can be applied to determine MTX sensitivity for the treatment of RA patients. However, further pharmacokinetics studies are required in this regard. ..
  46. Baggott J, Vaughn W, Hudson B. Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5'-adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole-4-carboxamide riboside and ribotide. Biochem J. 1986;236:193-200 pubmed
  47. Lyons S, Christopherson R. Antifolates induce primary inhibition of the de novo purine pathway prior to 5-aminoimidazole-4-carboxamide ribotide transformylase in leukemia cells. Biochem Int. 1991;24:187-97 pubmed
    ..MTX prevented azaserine-induced accumulation of FGAR polyphosphates. Hence, these antifolates induce primary inhibition of the de novo purine pathway at, or prior to, glycinamide ribotide transformylase (reaction 3). ..
  48. Borrell J, Teixido J, Matallana J, Martinez Teipel B, Colominas C, Costa M, et al. Synthesis and biological activity of 7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF) and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF). J Med Chem. 2001;44:2366-9 pubmed
    ..coliGARTFase-5-DATHF-GAR pointed to an electronic repulsion between the atoms of the 7-oxo group and the carbonyl group of Arg90 as a possible explanation for the inactivity of 18a-c. ..
  49. Boccalatte F, Voena C, Riganti C, Bosia A, D Amico L, Riera L, et al. The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL. Blood. 2009;113:2776-90 pubmed publisher
    ..Prediction of tumor responses to methotrexate may justify specific molecular-based chemotherapy. ..
  50. Saraf M, Moore G, Maranas C. Using multiple sequence correlation analysis to characterize functionally important protein regions. Protein Eng. 2003;16:397-406 pubmed
    ..In addition, we use our approach in a predictive fashion to identify important regions of a transmembrane amino acid transporter protein for which there is limited structural and functional information available. ..
  51. Hong S, Piper M, Sinclair D, Dawes I. Control of expression of one-carbon metabolism genes of Saccharomyces cerevisiae is mediated by a tetrahydrofolate-responsive protein binding to a glycine regulatory region including a core 5'-CTTCTT-3' motif. J Biol Chem. 1999;274:10523-32 pubmed
    ..Tetrahydrofolate or a derivative may act as a ligand for the transcription factor controlling expression of one-carbon metabolism genes. ..
  52. Su Y, Yamashita M, Greasley S, Mullen C, Shim J, Jennings P, et al. A pH-dependent stabilization of an active site loop observed from low and high pH crystal structures of mutant monomeric glycinamide ribonucleotide transformylase at 1.8 to 1.9 A. J Mol Biol. 1998;281:485-99 pubmed
    ..Thus, the pH-dependence of the enzyme activity appears to arise from local active site rearrangements and not from differences due to monomer-dimer association. ..
  53. Lobley C, Schmitzberger F, Kilkenny M, Whitney H, Ottenhof H, Chakauya E, et al. Structural insights into the evolution of the pantothenate-biosynthesis pathway. Biochem Soc Trans. 2003;31:563-71 pubmed
    ..We conclude that it is likely to have evolved via a patchwork mechanism, whereby the individual enzymes were recruited separately. ..