Ubiquitin Conjugating Enzyme

About Ubiquitin Conjugating Enzyme:

Ubiquitin-conjugating enzymes catalyze the second step of the ubiquitination reaction that enables the degradation of proteins via the proteasome.

Ubiquitin Conjugating Enzyme Mechanism
The purpose of the ubiquitin-conjugating enzyme is to help the cell recycle short peptide fragments.
The first step is to attach ubiquitin - a relatively short protein made of 76 amino acids - to the lysine on the target protein using a covalent reaction. Once the initial ubiquitin molecule is in place, and the protein has been tagged, it is then possible for the polyubiquitin chain to form. The proteasome’s 19S regulatory particle recognizes the chain. The proteasome recognizes the chain, triggering the unfolding of the target protein via ATP and allowing passage to the proteasome’s 20S core particle. Proteases then degrade the target into short peptide chains that the cell can use.

Ubiquitin Conjugating Enzyme Function
There are three classes of ubiquitin-related enzymes: E1, E2, and E3. All of these classes have different properties and operate in distinct ways in the body.
E1 is the least physiologically-regulated of all of the enzymes in this class. It activates ubiquitin using the ATP-dependent mechanism described in the previous section. The ATP-activated ubiquitins then bind to the protein substrate and degrade them using the ubiquitin-proteasome pathway. The process is not dependent on the substrate.
E2 ubiquitin-conjugating enzymes are believed to be more selective in their choice of target. Researchers initially thought that the purpose of E2 enzymes was simply to transfer ubiquitin to E3s. However, they may play a more active role. Current evidence suggests that E2s may be able to directly conjugate ubiquitin into substrates.
Unfortunately, a definitive answer to this question is likely a long way from being answers. E2s are structurally diverse and found in different forms across a range of species. In yeast, for instance, 13 genes encode for E2s. In mammals, there appears to be in the order of 25 to 30.
E3s are widely believed to be even more diverse than E2s. In combination, there is evidence that they may have a high degree of site-specificity, allowing them to work on a range of substrates without damaging surrounding tissue.
E3s are so diverse that they may use catalytic mechanisms not described above. Other possible chemical mechanisms could break proteins down into their peptide constituents.
Ubiquitin-conjugating enzymes should not be confused with ubiquitin-activating enzymes. Ubiquitin-activating enzymes are those described above that are not substrate-specific. Their role is to active the ubiquitin by covalently attaching the molecule to the protein site cysteine residue. Once that has occurred, it is then time for the E2 and E3 conjugating enzymes to take over the process. After conjugation, the E2 molecule binds to several of the ubiquitin ligases or the E3 via the unique binding region.
The job of the E3 ubiquitin-conjugating enzyme is to bind to the target protein substrate and then transfer the ubiquitin from the cysteine residue to a new lysine residue on the surface of the target protein.