Disease relevance of N-FORMYLMETHIONINE

• The Listeria peptide is digested by carboxypeptidase Y but resists aminopeptidase M, and only peptides with N-formyl methionine competitively block its presentation to CTL [1].
• Total synthesis of a RNA molecule with sequence identical to that of Escherichia coli formylmethionine tRNA [2].
• Methionine and formylmethionine specific tRNAs coded by bacteriophage T5 [3].
• H2-M3-restricted presentation of N-formyl methionine (f-Met) peptides to CD8(+) T cells provides a mechanism for selective recognition of bacterial infection [4].
• The amino terminus of the Salmonella typhimurium aspartate receptor has been identified as formylmethionine by mass spectral analysis of the amino-terminal tryptic peptide [5].

High impact information on N-FORMYLMETHIONINE

• MTF is derived from ND1, a mitochondrially encoded protein, and the amino-terminal N-formyl-methionine is essential for binding to HMT; conservative substitutions at the sixth residue causes MTF to be a minor H antigen [6].
• We generated mutants of Escherichia coli formylmethionine tRNA that have a base pair at the end of the acceptor stem [7].
• Escherichia coli formylmethionine tRNA: mutations in GGGCCC sequence conserved in anticodon stem of initiator tRNAs affect initiation of protein synthesis and conformation of anticodon loop [8].
• Anticodon loop size and sequence requirements for recognition of formylmethionine tRNA by methionyl-tRNA synthetase [9].
• The minor product had the complete coat protein sequence starting from formylmethionine except for a probable amino acid substitution at codon 7 (UAG) [10].

Chemical compound and disease context of N-FORMYLMETHIONINE

• We compared the template-dependent ribosome binding activities, in the presence of initiation factors, of wild type and anticodon sequence mutants of Escherichia coli initiator tRNAs that carry formylmethionine (fMet), formylglutamine (fGln), or formylvaline (fVal) [11].
• Polyuridylic acid-dependent binding of fMet-tRNA to Escherichia coli ribosomes and incorporation of formylmethionine into polyphenylalanine [12].
• The 3' end of the operon contains a 77-nucleotide (nt) N-formylmethionine (fMet) initiator tRNA-encoding gene with 100% sequence identity to the fMet tRNA-encoding gene of Rhodobacter sphaeroides [13].
• Using purified Staphylococcus aureus EF-P and a reconstituted Escherichia coli ribosomal system, an assay monitoring the addition of radiolabeled N-formyl methionine to biotinylated puromycin was developed [14].
• Modification of specific lysine residues in E. coli methionyl-tRNA synthetase by crosslinking to E. coli formylmethionine tRNA [15].

Biological context of N-FORMYLMETHIONINE

• These results suggest that the cytoplasmic protein-synthesizing system of yeast, like that of eubacteria, can at least to some extent utilize formylated initiator Met-tRNA to initiate protein synthesis and that initiation of proteins with formylmethionine leads to the slow-growth phenotype [16].
• Alteration of the kinetic parameters for aminoacylation of Escherichia coli formylmethionine transfer RNA by modification of an anticodon base [17].
• Interestingly, the formylmethionine tRNA hybridizes to two loci within one of these gene clusters [18].
• The nucleotide sequence of formylmethionine tRNA from Mycoplasma mycoides sp. capri [19].
• Reversible inactivation of Escherichia coli methionyl-tRNA synthetase by covalent attachment of formylmethionine tRNA to the tRNA binding site with a cleavable cross-linker [20].

Anatomical context of N-FORMYLMETHIONINE

• Di- and tripeptides containing formylmethionine are strong attractants for both neutrophils and macrophages, whereas the corresponding nonacylated compounds are not chemotactic [21].
• The activity of these oligomers in RF-1-dependent termination was assayed by the release of analogues of peptides, N-acetyl or N-formyl-methionine, that were bound to ribosomes as N-acetyl or N-formyl-Met-tRNAfMet with either AUG or AUG covalently linked to another oligoribonucleotide [22].
• Murine infection with the Gram-positive intracellular bacterium Listeria monocytogenes activates CD8(+) T cells that recognize bacterially derived N-formyl methionine peptides in the context of H2-M3 MHC class Ib molecules [23].
• The amino terminus of the aspartate chemoreceptor is formylmethionine [5].
• In this procedure, the NH2 termini of nascent peptides are blocked by incorporating labeled formylmethionine instead of methionine, using yeast initiator tRNA in the wheat germ cell-free system [24].

Associations of N-FORMYLMETHIONINE with other chemical compounds

• Polyethylene glycol is shown to be a competitive inhibitor with a KI value of 6 mM with respect to formylmethionine under conditions similar to those used for crystallization [25].
• Unlike calcium ionophore, however, pretreatment of basophils with diatrizoate may also induce dose-dependent inhibition of reactivity during subsequent challenges with anti-IgE, N-formyl methionine peptide, and calcium ionophore [26].
• Here we show that the reaction of P-site formylmethionine (fMet)-tRNA(fMet) with a modified A-site tRNA substrate, Phelac-tRNA(Phe), in which the nucleophilic amino group is replaced with a hydroxyl group, does not show the pH dependence observed with small substrate analogs such as puromycin and hydroxypuromycin [27].

Gene context of N-FORMYLMETHIONINE

• VP1, VP2, and vp3 were all labeled with [35S] formylmethionine when they were synthesized in the presence of [35S] formylmethionyl-tRNAfmet [28].
• Expression of Escherichia coli methionyl-tRNA formyltransferase in Saccharomyces cerevisiae leads to formylation of the cytoplasmic initiator tRNA and possibly to initiation of protein synthesis with formylmethionine [16].
• Galectin expression was up-regulated in inflammatory and activated macrophages, revealing a significant increase in phorbol ester- and formylmethionine oligopeptide-treated cells [29].
• The H2-M3 class Ib gene product, M3, preferentially presents formylmethionine-initiating (fMet) peptides derived from the N termini of bacterial and mitochondrial proteins [30].
• In order to cleave RNA at specific positions in Escherichia coli formylmethionine tRNA, RNase H and complementary chimeric oligonucleotides consisting of DNA and 2'-O-methyl-RNA (Inoue et al [31].

Analytical, diagnostic and therapeutic context of N-FORMYLMETHIONINE

• The molecular mass of 3,794 Da as determined by MALDI-MS and by ESI requires the N-terminal methionine to be formylated and is in good agreement with the value calculated from the formylmethionine containing sequence (3,766.5 Da + 28 Da = 3,794.5 Da) [32].

References