E1 Activating

Ub and UBL-dependent metabolism is a multi-enzyme process involving the successive activities of distinct conjugating enzymes. The E1 activating enzymes are central to ubiquitin or ubiquitin-like modifier (UBL) conjugation in vivo and in vitro since they initiate the cascade of conjugation by activating their respective modifiers. Each activating enzyme works in a parallel, but distinct way. The E1 for UBL NEDD8 will not activate SUMO, for example. Each enzyme catalyzes the reaction of ATP and Ub or UBL to activate the C-terminus of the modifier with a high energy thiolester bond. It is this high energy bond that is then transferred to the E2 carrier enzyme for the modifier for the next step in conjugation.