Abstract
Adenosylcobalamin-dependent enzymes tend to inactivate holoenzyme accompanying the modification of the coenzyme. We identified reactivating factors for inactivated holoenzymes of adenosylcobalamin-dependent diol dehydratase (DD), glycerol dehydratase (GD), and ethanolamine ammonia-lyase (EAL), i.e., DDR, GDR, and EALR, respectively. DDR hydrolyzes ATP to ADP and induces its conformational change. Then, DDR facilitates the dissociation of the damaged coenzyme from the inactivated holoDD through formation of tight DD-DDR-ADP complex. This complex is dissociated into apoDD and DDR by replacing ADP on DDR with ATP, and then active holoenzyme is reconstituted. Crystal structures of DDR allow us to construct a model of DD-DDR complex. DD should be bind to DDR with concomitant displacement of a DDR β subunit by a DD β subunit. It induces steric repulsion between DD α and DDR α subunits that would lead to the release of a damaged coenzyme from inactivated holoDD. GDR reactivates inactivated holoGD by similar mechanism.
