Ubiquitin activating enzymes are 'canonical' E1 enzymes that activate ubiquitin for subsequent steps along the ubiquitin conjugation cascade. They perform three distinct chemical reactions: first, they bind ATP, magnesium and ubiquitin to catalyze formation of a high-energy acyl adenylate intermediate with subsequent release of pyrophosphate; second, an E1 catalytic cysteine attacks the ubiquitin-adenylate to catalyze formation of a high-energy thioester bond between the E1 and ubiquitin and release of the AMP product; finally, the E1-ubiquitin catalyzes transthioesterification to an E2 to form a high energy thioester-linked E2-ubiquitin product. (Adapted from
PMID:28234446.)
