Question

Describe the biochemical function of the \(\mathrm{E} 1, \mathrm{E} 2,\) and E3 enzymes in the ubiquitinating system. Why are there -500 E3 genes in the human genome but only two E1 genes?

Short answer

Answer: The biochemical functions of E1, E2, and E3 enzymes in the ubiquitination system are as follows: E1 activates ubiquitin by attaching to it using a thioester bond, E2 transfers the activated ubiquitin from E1 to its active site cysteine, and E3 is responsible for transferring the activated ubiquitin from E2 to the target protein, ensuring specificity. There are more E3 genes than E1 genes in the human genome because E3 enzymes are in charge of target protein recognition and binding, which requires high specificity and versatility. Having numerous E3 genes allows the ubiquitination system to target a wide range of proteins and regulate various biological processes.

Step-by-step solution

Understand and Describe Ubiquitination System

The ubiquitination system is an essential cellular process responsible for regulating the degradation, localization, and activity of proteins. It involves the covalent attachment of ubiquitin, a small protein, to target proteins. The process is carried out through a three-enzyme cascade system composed of E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin ligase) enzymes.

Biochemical Function of E1 Enzyme

The E1 enzyme plays a role in activating ubiquitin. The specific function of E1 is to bind with ubiquitin in an ATP-dependent manner, forming a thioester bond between its active site cysteine residue and the C-terminal glycine of ubiquitin. By activating ubiquitin, E1 enzyme initiates the ubiquitination process.

Biochemical Function of E2 Enzyme

The role of the E2 enzyme is to transfer the activated ubiquitin from E1 to its active site cysteine, creating a new thioester bond. This transfer is crucial for the progression of the ubiquitination process, as it prepares the activated ubiquitin for its final destination.

Biochemical Function of E3 Enzyme

The E3 enzyme serves the purpose of transferring the activated ubiquitin from the E2 enzyme to the target protein. It plays a crucial role in recognizing and binding to the target protein, ensuring the specificity of the ubiquitination process. The E3 enzyme forms an isopeptide bond between the activated ubiquitin's C-terminal glycine and the lysine residue in the target protein.

Reason for the Difference in Number of E1 and E3 Genes

There are only two E1 genes in the human genome because the E1 enzyme's primary function, activating ubiquitin, is a conserved process that doesn't require much variation. In contrast, there are approximately 500 E3 genes in the human genome because the E3 enzyme is responsible for target protein recognition and binding, which requires high specificity and versatility. The numerous E3 genes allow the ubiquitination system to target a wide range of proteins within the cell and regulate different biological processes.