Release of a damaged cofactor from a coenzyme B₁₂-dependent enzyme: X-ray structures of diol dehydratase-reactivating factor

The crystal structures of ADP bound and nucleotide-free forms of molecular chaperone-like diol dehydratase-reactivating factor (DDR) were determined at 2.0 and 3.0 Å, respectively. DDR exists as a dimer of heterodimer (αβ)₂. The α subunit has four domains: ATPase domain, swiveling domain, linker domain, and insert domain. The β subunit, composed of a single domain, has a similar fold to the β subunit of diol dehydratase (DD). The binding of an ADP molecule to the nucleotide binding site of DDR causes a marked conformational change of the ATPase domain of the α subunit, which would weaken the interactions between the DDR α and β subunits and make the displacement of the DDR β subunit by DD through the β subunit possible. The binding of the DD β subunit to the DDR α subunit induces steric repulsion between the DDR α and DD α subunits that would lead to the release of a damaged cofactor from inactivated holoDD.