E1, also known as an ubiquitin-activating enzyme, catalyzes the first step in the ubiquitination reaction. In addition to E1s of ubiquitination, E1s also represents E1s of ubiquitin-like modification (1). At the start of the conjugation cascade, the E1 enzyme binds ATP-Mg2+ and ubiquitin or ubiquitin-like, and catalyses ubiquitin or ubiquitin-like C-terminal acyl adenylation. In the next step a catalytic cysteine on the E1 enzyme attacks the ubiquitin-AMP or ubiquitin-like-AMP complex through acyl substitution, simultaneously creating a thioester bond and an AMP leaving group. Finally, the E1~ubiquitin or E1~ubiquitin-like complex transfers ubiquitin or ubiquitin-like to an E2 enzyme, respectively. This pathway repeats itself until the target protein has a full chain of ubiquitin or ubiquitin-like attached to itself (2).

1. http://en.wikipedia.org/wiki/Ubiquitin-activating_enzyme

2. Schulman, B.A. and Harper, J.W. (2009) Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat. Rev. Mol. Cell Biol., 10, 319-331. PMID: 19352404