Ubiquitin catalysis mechanism

Beeleth, E. S. and Pickart, C. M. Mechanism of ubiquitin conjugating enzyme E2—230K catalysis involving a thiol relay Biochemistry 1995, 35, 1664-71. 

Even with the uncertainty in E2 active-site position, the models have suggested that there would be no E3 residues near the E2 active site, in agreement with the observations made in the c-Cbl-E2 structure. This again ruled out the possibility that the SCF E3 provides acid/base catalysis and the possibility that the SCF positions the -amino group of the lysine at the E2 active site [66]. The only plausible mechanism left accounting for the catalysis mediated by the SCF in substrate ubiq-uitination is that the E3 complex helps increase the effective concentration of a portion of the substrate that contains the physiological ubiquitination-site lysine at the E2 active site. This model made the testable prediction that the distance between the destruction motif and the ubiquitinated lysine is a determinant of the ubiquiti-nation efficiency. 

ULPs are still classified as DUBs because the function and mechanism of catalysis is so similar to those of the DUBs that act on ubiquitin. ULPs lack significant sequence homology to other DUBs and are more closely related to viral proteinprocessing proteases [39]. 

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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