Structural and mechanistic comparisons of the metal-binding members of the vicinal oxygen chelate (VOC) superfamily

The vicinal oxygen chelate family of enzymes catalyzes a highly diverse set of chemistries that derives from one common mechanistic trait: bidentate coordination to a divalent metal center by a substrate or intermediate or transition state through vicinal oxygen atoms. The array of reactions catalyzed by this family is mediated structurally by a common fold and protein-chelating residues that secure and localize a metal ion. The common fold has topological symmetry being comprised of two βαβββ units that form an incompletely closed barrel of β-sheet about the metal ion. Interestingly, despite the diversity of the reactions catalyzed and the large number of metals observed to bind and promote the chemistry, this semi-symmetrical open barrel extends metal liganding side chains inward from a highly positionally conserved constellation of amino acid residues within the structure. Moreover, the core barrel fold arises from an array of possible intra/inter domain and subunit arrangements of the individual βαβββ units that are universally observed to stack side-by-side contacting along the first β-strand of each. While there are examples of enzymes that use this fold and do not bind a metal ion, this review is concerned with summarizing the key structural and mechanistic correlations that can be made for the metal-dependent vicinal oxygen chelate enzyme family members.

The vicinal oxygen chelate enzymes share a semi-symmetrical secondary structure arrangement about the active site that is associated with a divalent metal ion. This simple duplicated βαβββ motif imparts one common mechanistic attribute to the family, the ability to bind a vicinal oxygen pair at some stage in catalysis.Figure optionsDownload as PowerPoint slide