NEDD8 activating enzymes are 'canonical' E1 enzymes that act as heterodimers to activate the ubiquitin-like protein NEDD8 for subsequent steps along the NEDD8 conjugation cascade. They perform three distinct chemical reactions: first, they bind ATP, magnesium and NEDD8 to catalyze formation of a high-energy acyl adenylate intermediate with subsequent release of pyrophosphate; second, an E1 catalytic cysteine attacks the NEDD8-adenylate to catalyze formation of a high-energy thioester bond between the E1 and NEDD8 and release of the AMP product; finally, the E1-NEDD8 catalyzes transthioesterification to an E2 to form a high energy thioester-linked E2-NEDD8 product. (Adapted from
PMID:28234446.)
