Disease relevance of N-formyl-L-methionine

• Translation of poliovirus RNA in vitro: studies on n-formylmethionine-labeled polypeptides initiated in cell-free extracts prepared from poliovirus infected HeLa cells [1].
• This was also confirmed by incubating p2 with tRNA(fMet)Met (fMet, N-formylmethionine) from Escherichia coli: the hydrolysis products were thus identified as 3'-phosphooligonucleotides [2].

High impact information on N-formyl-L-methionine

• Bacteria similarly initiate protein synthesis with N-formylmethionine; indeed, we established that Hmt can also present prokaryotic peptides in an N-formyl-dependent manner [3].
• Like bacteria, mitochondria initiate protein synthesis with an N-formylmethionine residue [4].
• Elongation factor P (EFP) is a protein that stimulates the peptidyltransferase activity of fully assembled 70 S prokaryotic ribosomes and enhances the synthesis of certain dipeptides initiated by N-formylmethionine [5].
• Cross-recognition of N-formylmethionine peptides is a general characteristic of H2-M3-restricted CD8+ T cells [6].
• Peptide deformylase (PDF) is an essential bacterial metalloenzyme which deformylates the N-formylmethionine of newly synthesized polypeptides and as such represents a novel target for antibacterial chemotherapy [7].

Biological context of N-formyl-L-methionine

• A peptide consisting of the 17 N-terminal amino acids of native bovine rhodanese in combination with the chaperone DnaJ specifically inhibits release factor- and stop codon-dependent hydrolysis of N-formylmethionine from N(formyl)-methionyl-tRNA bound with AUG to salt-washed ribosomes [8].
• Comparison of the amino acid sequence with the recently published sequence of the gene encoding the cytochrome b apoprotein suggests that the N-formylmethionine is removed [9].
• OBJECTIVE: The aim of this study was to determine the effect of corticosteroids on the increase in airway microvascular permeability (MVP) and airway resistance induced by N-formylmethionine leucyl-phenylalanine in the rabbit [10].
• Methylprednisolone reduces airway microvascular permeability but not airway resistance induced by N-formylmethionine leucyl-phenylalanine in the rabbit [10].

Anatomical context of N-formyl-L-methionine

• Leucocyte or platelet N-formylmethionine deformylase may be important in modulation of neutrophil responses to chemoattractant formylmethionyl peptides or similar compounds [11].
• H2-M3-restricted CD8+ T cells can exhibit cross-reactivity to different bacterially derived N-formylmethionine peptides [6].
• Addition of TD beta gamma isolated from TD prepared with GTP[S] (TD beta gamma GTP[S]) to HL 60 membranes abolished high-affinity binding of fMet-Leu-[3H]Phe (fMet, N-formylmethionine) to its receptor [12].
• Membranes of myeloid differentiated human leukemia (HL 60) cells contain receptors for the chemotactic peptide, fMet-Leu-Phe (fMet, N-formylmethionine), interacting with pertussis-toxin-sensitive guanine-nucleotide-binding proteins (G proteins) [13].

Associations of N-formyl-L-methionine with other chemical compounds

• The alpha subunits of Gi (Gi alpha) and Gs (guanine-nucleotide-binding proteins involved in adenylate cyclase inhibition and stimulation, respectively) was ADP-ribosylated by cholera toxin in differentiated HL-60 cell membranes upon stimulation of chemotactic receptors by fMLF (fM, N-formylmethionine) [14].
• Short-term exposure (12 seconds) to the peptide n-formylmethionine leucyl-phenylalanine (FMLP, 1 microM) also elevated neutrophil cyclic AMP accumulation [15].

Gene context of N-formyl-L-methionine

• The results indicated that only partial N-terminal processing was occurring in vitro and that the first residue of the unprocessed NADH dehydrogenase is N-formylmethionine [16].
• Increased peptide deformylase activity for N-formylmethionine processing of proteins overexpressed in Escherichia coli: application to homogeneous rubredoxin production [17].
• PDF is an essential bacterial metalloenzyme that deformylates the N-formylmethionine of newly synthesized bacterial polypeptides [18].

Analytical, diagnostic and therapeutic context of N-formyl-L-methionine

• A specific enzyme for the liberation of N-terminal N-formylmethionine from N-formylmethionyl peptides was purified 4750-fold from rat liver by successive applications of (NH4)SO4 precipitation, DEAE-cellulose, N-formylbestatin-AH-Sepharose 4B and AH-Sepharose 4B chromatography followed by Sepharose CL-6B gel filtration [19].

References