Miscellaneous protein synthesis inhibitors

Protein synthesis inhibitors include many different classes of medications that prevent bacterial ribosomes from synthesizing proteins. The ones that target the 50S subunit of the ribosome include chloramphenicol, macrolides, lincosamides, and oxazolidinones.

Okay, first, let’s look at how genes become proteins. There’s two steps: transcription and translation. During transcription, a specific gene on the DNA is “read” and a copy is made called a messenger RNA, or mRNA, which is like a blueprint with instructions on what protein to build. Translation is also known as protein synthesis, and it’s when organelles called ribosomes assemble the protein from amino acids within the cytoplasm.

Now, prokaryotic cells, like bacteria, have smaller ribosomes than eukaryotic cells, like those found in humans. Bacterial ribosomes are made up of a 50S subunit and a 30S subunit which combine to form a 70S ribosome. Eukaryotic ribosomes are made up of a 60S and a 40S subunit that form a 80S ribosome. Since these proteins are different, we can create medications that selectively interfere with the bacterial ones.

Protein synthesis involves initiation, elongation, and termination. In bacteria, initiation occurs when the 50S and 30S subunits bind to the mRNA sequence to form a ribosome-mRNA complex, also called the initiation complex. The mRNA serves as a blueprint for the protein that will be synthesized. It’s made up of three nucleotide-long sequences, called codons, on top of which transport RNA, or tRNA, carrying amino acids can bind with their matching anticodon. The complete ribosome has 3 sites where tRNA can enter and bind. These are called the A, or aminoacyl site, the P, or peptidyl site, and the E, or exit site.

Elongation starts when the first tRNA, carrying a formylmethionine amino acid, enters the P site and binds to the start codon. This causes a conformational change which unlocks the A site for the next tRNA. The next tRNA binds at the A site, the amino acid detaches from the tRNA in the P site, and a peptide bond is formed by an enzyme called peptidyl transferase between the amino acids in the P and A sites, a process known as transpeptidation. Now, the A site has the newly formed peptide chain dangling from it, while the P site has an empty tRNA with no amino acids. In the final stage of elongation, the tRNA in the P site slides over to the E site, and the tRNA in the A site slides over to the P site. The ribosome slides over so the free A site is over the next codon on the mRNA and this process is called translocation. Next, a new tRNA with the matching anticodon binds, and the process repeats until a long peptide chain called a protein is synthesized.