PMC

Structures of E1-ubiquitin activating enzyme inhibitors.

Superposition between the human E1 model and yeast E1 template (human E1 in green; yeast E1 in red).

Superposition of the SCCH domains from the model of human and mouse E1 (human E1 in red; mouse E1 in green).

Model of human E1 in complex with ubiquitin viewed from different angles (90° rotation). The E1 model is represented in red; ubiquitin is represented in green.

Superposition of free and E1-bound ubiquitin (bound mouse ubiquitin in red; free human ubiquitin in green). The binding of ubiquitin to E1 introduces a significant shift at the ubiquitin C-terminus.

Sequence alignment between human E1, yeast E1 (PDB: 3CMM) and mouse E1 (PDB: 1Z7L). Represented in red are the residues that define the ubiquitin binding site.

Molecular dynamics simulation plots. On the left is the energy variation during the simulation. On the right is the RMSD variation during the simulation (in red the RMSD value of each step compared to the previous one; in cyan the RMSD value of each step compared to the initial step).

Interactions between ubiquitin c-terminus and E1. Hydrogen bonds are represented as arrows (green: side chain hydrogen bond; blue: backbone hydrogen bond). Blue areas indicate the exposition of the residue to the external solvent. Note the cation-aromatic interaction between Arg72 of ubiquitin and Tyr 571 of E1.

Schematic overview of the role of ubiquitin-activating enzyme, E1. The E1 reaction sequence begins with adenylation of a free ubiquitin molecule with concomitant ATP hydrolysis. The adenylated ubiquitin is then transferred to the active site cysteine residue of E1, followed by transfer to the active site cysteine residue of an E2 ubiquitin ligase, the next enzyme in the catalytic chain.