Question

What is the role of activated esters in ribosomal protein synthesis and in serine protease-catalyzed peptide hydrolysis?

Answer 1

In serine protease catalysed protein hydrolysis, activated ester is formed when the carbonyl carbon of the splitted peptide fragment is linked to the serine residue through ester linkage

The role of the activated esters in serine protease is that when the carboxyl end of the splitted peptide is linked to the serine residue of the serine protease. The carbonyl carbon of the peptide acts as a strong electrophile and attacks the lone pair of oxygen of the water molecule. This makes its linkage with the serine residue weak an finally breaks away from the enzyme as a peptide fragment.

In short activated ester helps in breakdown of protein by serine protease by increasing the electrophilicity of the carbonyl carbon towards water molecule.

In ribosomal protein synthesis the ester is formed when amino acid is linked through its carboxyl group with the tRNA molecule. This tRNA molecule then holds the entire newly synthesized peptide chain in the ribosome, when present at the P-Site of the ribosome. The carboxyl group of the peptide chain acts as a strong electrophile when linked to tRNA at P-Site through ester linkage thus is activated. The strong electrophilicity of the carbonyl carbon makes it to attack the N atom of the amino group of the amino acid linked to tRNA molecule present at the A-Site of the ribosome. This electrophilic attack of the Carbonyl carbon makes its linkage with the tRNA at P-Site weak and finally breaks and the newly synthesized peptide chain is now linked to the tRNA molecule at A-Site. Which later slides to P- Site.

Thus activated ester in ribosomal protein synthesis helps the carbonyl carbon to attack the lone pair of the N of the amino group of the incoming amino acid by increasing the electrophilicity of the carbonyl carbon.