Heme Oxygenase-Like Metalloenzymes

Area of Science:

• Biochemistry and enzymology
• Protein superfamily characterization
• Bacterial metabolism

Background:

• Heme oxygenase (HO)-like metalloenzymes represent an emerging protein superfamily.
• These enzymes are primarily found in bacterial biosynthetic pathways and share conserved features with the heme catabolic enzyme, HO.
• They possess a flexible protein scaffold and metal-binding residues, accommodating various cofactors like diiron, manganese-iron, and mononuclear iron.

Purpose of the Study:

• To explore the diverse reaction outcomes and mechanisms of HO-like metalloenzymes.
• To understand the role of the HO-like scaffold in cofactor assembly, disassembly, and reactivity.
• To investigate the potential of these enzymes in catalyzing unprecedented fragmentation and rearrangement reactions.

Main Methods:

• Analysis of conserved protein scaffolds and metal-binding residues.
• Characterization of cofactor assembly, including diiron, manganese-iron, and mononuclear iron clusters.
• Investigation of the reaction mechanism in canonical HO-like diiron oxygenases/oxidases (HDOs), focusing on the peroxo-Fe2(III/III) intermediate.

Main Results:

• HO-like metalloenzymes exhibit diverse reaction capabilities and mechanisms.
• The canonical HDOs utilize a diiron cluster that reacts with O2 to form a peroxo-Fe2(III/III) intermediate.
• The HO-like scaffold provides unique metal-binding properties and reactivity, enabling dynamic cofactor management.

Conclusions:

• The HO-like scaffold confers distinctive metal-binding properties and unusual reactivity to its metallocofactor.
• These enzymes are capable of mediating fragmentation and rearrangement reactions, unprecedented in other dinuclear iron enzymes.
• Significant unexplored sequence space within the HO-like metalloenzyme superfamily offers potential for discovering novel mechanisms and reactivities.