Heme Oxygenase–Like Metalloenzymes
Sarah R. Pope, Molly J. McBride, Mrutyunjay A. Nair, Xavier E. Salas-Solá, Carsten Krebs, J. Martin Bollinger, Amie K. Boal
Abstract
Heme oxygenase (HO)-like metalloenzymes are an emerging protein superfamily diverse in reaction outcome and mechanism. Found primarily in bacterial biosynthetic pathways, members conserve a flexible protein scaffold shared with the heme catabolic enzyme, HO, and a set of metal-binding residues. Most HO-like metalloenzymes assemble a diiron cluster, although manganese-iron and mononuclear iron cofactors can also be accommodated. In the canonical HO-like diiron oxygenases/oxidases (HDOs), an Fe 2 (II/II) complex reacts with O 2 to form a peroxo-Fe 2 (III/III) intermediate ( P ), common to all HDOs studied to date. The HO-like scaffold confers both distinctive metal-binding properties, allowing for dynamic cofactor assembly and disassembly, and unusual reactivity to its associated metallocofactor. These features may prove to be important in HDO-mediated catalysis of the fragmentation and rearrangement reactions that remain unprecedented among other dinuclear iron enzymes. Much of the sequence space in the HO-like metalloenzyme superfamily remains unexplored, offering exciting opportunities for the discovery of new mechanisms and reactivities.