Title : New discoveries on monofunctional catalases
Catalases (EC 188.8.131.52) are redox enzymes responsible for the dismutation of H2O2 into water and molecular oxygen. These metalloproteins are found in aerobic organisms and play a crucial role in prokaryotic and eukaryotic cell detoxification. Catalases have been studied for over 100 years, with examples of the enzyme isolated, purified and characterized from many different organisms. The crystal structures of 15 heme-containing catalases have now been solved, revealing a common, highly conserved core in all enzymes. The active centre consists of a haem with a tyrosine ligand on the proximal side and a conserved histidine and an aspartate flanking the putative peroxide-binding site on the distal side. Three channels, the main channel oriented perpendicular to the plane of the haem, the lateral channel approaching the plane of the haem and the central channel leading from the distal side of the haem to the central cavity, connect the deeply buried active site to the exterior of the enzyme. The main channel is believed to be a primary route for the access of peroxide to the active site. The lateral or minor channel approaches the haem from above, adjacent to the essential asparagine, and emerges on the enzyme surface at a location corresponding to the NADP(H)-binding pocket in catalases that bind a nicotinamide cofactor. The function of this channel remains unknown, although molecular-dynamics simulations suggest that water can exit the protein through this channel. Although catalases have been studied for many years, a peroxide independent oxidative activity of catalases has recently been recognized. For example, Scytalidium thermophilum catalase (CATPO) has been shown to oxidize o-diphenolic and some p-diphenolic compounds in the absence of hydrogen peroxide. This peroxide independent secondary activity of catalases has also been identified in other catalases (mammalian catalase and catalases from Aspergillus niger, Corynebacterium glutamicum, Thermobifida fusca and Amaranthus cruentus) and has been presumed to also occur at the heme active site. Based on structural, mutation and kinetic data, the pocket at the entrance to the lateral channel has been identified as the site of both oxidase substrate and catalase inhibitors. Peroxide independent phenolic substrate oxidation is then likely to occur in a similar manner to NADPH oxidation, via electron transfer from the substrate to a high-valent iron–oxo intermediate, presumably formed via reaction with oxygen.
Presentation Learning Outcome
- Follow the latest discoveries on catalase function
- Examine protein crystallography techniques
- Explain the significance of protein structure for understanding the enzymatic catalytic mechanism(s)
- Explain the structure-function analysis of catalases