Biochemistry/Peptide Bond Formation
The biochemical mechanism of peptide bond formation is below. For a more chemical description, please consult the Organic Chemistry textbook.
Note: As with any biochemical mechanism, the following is enzyme-catalyzed and does not occur spontaneously in the cell. Enzyme active sites are left out for clarity.
The addition of a the amino-terminus of an amino acid to the carboxy-terminus of a second amino acid goes through two primary steps:
- Carboxylate Activation
- Nucleophilic Addition/Formation of the tetrahedral intermediate
- Collapse of the tetrahedral intermediate
The carbonyl lone pair of the carboxy-terminal carbonyl attacks the terminal phosphate on a molecule of ATP via an SN2 reaction. The ADP acts as a leaving group, and the hydroxyl group on the carboxylate donates into the forming carbocation. Finally, the new carbonyl on the now phosphate ester is deprotonated.
The lone pair of the amino-terminus on the second amino acid attacks the carbonyl carbon of the phosphate ester, forming a tetrahedral intermediate with four substituents on the former carbonyl carbon: the oxylate ion, the phosphate, the nucleophile, and the alpha carbon of the first amino acid. Finally, the amine nucleophile is deprotonated to a neutral state.
Collapse of the tetrahedral intermediate
A lone pair on the oxylate ion collapses on the phosphate carbon, and the inorganic phosphate is lost as a leaving group. The resulting bond is an amide bond between the carbonyl carbon and the amine group.