Fmet

N-Formylmethionine (fMet) is a derivative of the amino acid methionine, distinguished by the addition of a formyl group to the amino terminus. This modification is significant in the initiation of protein synthesis in bacteria, mitochondria, and chloroplasts. fMet plays a crucial role in the early stages of protein synthesis by serving as the first amino acid incorporated into nascent proteins during the initiation process in these organisms. Its unique structure allows it to be recognized by specialized initiation factors that are not used for other amino acids, making it essential for the proper initiation of protein synthesis.

Biosynthesis and Function

The biosynthesis of fMet begins with the modification of methionine. The enzyme transformylase adds a formyl group to methionine, converting it into N-formylmethionine. This process is critical in prokaryotes and in the organelles of eukaryotes that are of prokaryotic origin, such as mitochondria and chloroplasts, reflecting the evolutionary heritage of these organelles.

In the context of protein synthesis, fMet is recognized by a specific tRNA, known as tRNA^fMet, which is charged with fMet by a specific aminoacyl-tRNA synthetase. This charged tRNA^fMet is then directed to the ribosome's P site, where it initiates the assembly of a polypeptide chain. The inclusion of fMet at the beginning of a protein is a unique feature of bacterial, mitochondrial, and chloroplastic proteins. In bacteria, the formyl group of fMet is usually removed after the synthesis of the protein by peptide deformylase, and the methionine may also be excised by a methionine aminopeptidase.

Role in Immune Response

fMet plays a significant role in the immune response. The human immune system can recognize bacterial fMet as a marker of bacterial infection. Leukocytes have receptors that specifically bind to fMet-containing peptides, which are absent in eukaryotic cells. This recognition helps to direct the immune response towards bacterial pathogens, making fMet a critical molecule in the innate immune system.

Clinical Significance

Given its unique presence in bacteria and its role in initiating protein synthesis, fMet has been explored as a target for antibiotic development. Compounds that can inhibit the formation of fMet-tRNA^fMet complex or interfere with its incorporation into proteins could potentially serve as antibiotics by specifically targeting bacterial protein synthesis while sparing eukaryotic cells.

See Also

• Protein synthesis
• Methionine
• Ribosome
• Aminoacyl-tRNA synthetase
• Immune system