InterPro domain: IPR042063

The E1 enzyme that catalyses carboxy-terminal Ub adenylation, thioester bond formation to a catalytic cysteine in the E1 Cys domain, together with thioester transfer to a catalytic cysteine in E2 conjugating enzymes are responsible for the Ubiquitin (Ub) conjugation initiation [ 1 ]. There are several homologues of this enzyme with one of them being ThiF [ 2 ].

The catalytic cysteine domain contains the E1 active site cysteine, and is divided in two half-domains, FCCH and SCCH, for 'first' and 'second' catalytic cysteine half-domain, respectively. This superfamily represents the domain 5 found in Ub-activating enzyme E1, the SCCH in which resides the catalytic cysteine [ 3 ]. This domain has an alpha-helical structure and likely to exist in equilibrium of open (adenylation active) and closed (thioester bond formation active) conformations. SCCH, FCCH (the first catalytic cysteine half-domain) and UFD (ubiquitin fold domain) are connected to the AAD (active adenylation domain) through flexible loops that allow the conformational changes and rotations of these domains essential for catalysis of Ub activation and transfer of activated UB from E1 to E2 [ 4 ].

1. Structure of a ubiquitin E1-E2 complex: insights to E1-E2 thioester transfer. Mol. Cell 49, 884-96
2. Natural history of the E1-like superfamily: implication for adenylation, sulfur transfer, and ubiquitin conjugation. Proteins 75, 895-910
3. Crystal structure of a human ubiquitin E1-ubiquitin complex reveals conserved functional elements essential for activity. J Biol Chem 293, 18337-18352