Ub-conjugating enzyme

It is of interest to know how polyUh is attached to target proteins This is achieved through the consecutive action of four enzymes (Fig. 6-8). In the first stage, (Uh-activating enzyme) is linked to Ub via a thioester bond in an ATP-dependent reaction. The Uh is then transferred to 2 (Ub-conjugating enzyme). The Ub is... 

Figure 23.3. Ubiquitin Conjugation. The ubiquitin-activating enzyme El adenylates ubiquitin (Ub) and transfers the ubiquitin to one of its ovm cysteine residues. Ubiquitin is then transferred to a cysteine residue in the ubiquitin-conjugating enzyme E2. Finally, the ubiquitin-protein ligase E3 transfers the ubiquitin to a lysine residue onthe target protein.

Fig. 2.9 Ubiquitinylation of proteins and degradation in the proteosome. Ubiquitin (Ub) is initially activated by an enzyme El, whereby the C-terminal carboxyl group of ubiquitin becomes attached to an SH group of El via a thioester bond. The activated ubiquitin is then transferred from El-Ub to the ubiquitin-conjugating enzyme, E2. Finally, the ubiquitin is covalently attached to the target protein in a reaction catalyzed by the E3 ubiquitin ligase. Re-...

In a transacylation reaction, the ubiquitin moiety is transferred from El-Ub to a cysteine-SH within the active site of of the ubiquitin-conjugating enzyme E2 to form E2-Ub. 

After the linkage of Ub to the substrate protein, a polyubiquitin (multiubiquitin) chain is often formed, in which the C-terminus of each ubiquitin unit is linked to a specific Lys residue (most commonly Lys48) of the previous Ub. The multiubiquitin-chain assembly is a processive reaction that usually requires only El, E2 and E3. However, an efficient multiubiquitination needs an additional conjugation factor termed E4 enzyme (Hoppe, 2005). Ubiquitin-protein ligases are, directly or indirectly, those that bind specific protein substrates, promote the transfer of Ub, and form a thioester intermediate to amide linkages with proteins or polyubiquitin chains. 

The second instance of ubiquitin conjugation in PRR involves an atypical poly-Ub chain and a novel mechanism of catalysis employing a Ubc enzyme variant (Uev), Mms2. The MMS2 gene was isolated by functional... 

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