Meta-Biol

• Pathways

After covalent attachment of the first NEDD8 molecule to the catalytic cysteine, a second NEDD8 binds to the now-free adenylation site on the UBA3 subunit of UBA3:NAE1. This 'doubly-loaded' E1 enzyme is primed to transfer the covalently-bound NEDD8 to the downstream E2 enzyme (Huang et al, 2005; Huang et al, 2007; reviewed in Enchev et al, 2015). Note that although not depicted here, the second NEDD8 moiety is covalently adenylated at its C-terminal glycine residue at the end of this reaction.