KatGs, the family of heme-containing enzymes named after their encoding katG gene, are homodimers, each organized in two subunits (N- and C-terminal) and with only the N-terminal having the heme active site. Yet the surface interactions with the C-terminal appear to have a long-range effect on the active site in the N-terminal. Disproportionation of hydrogen peroxide proceeds via the heme site (catalase activity), yet the mechanism differs from mono-functional catalases due to structural differences of the heme microenvironment. We have shown that the peroxidase reaction of KatGs involves Trp radicals as alternative intermediates, formed by intramolecular e- transfer. The crowded heme environment in KatGs precludes a substrate binding site close to the heme (as in peroxidases), thus the reaction with substrates proceeds either through long-range e- tranfer from the [Fe(IV)=O Por●+] intermediate or the [Fe(IV)=O Trp●] intermediates. We have also shown that specific Trp sites play a crucial role as e- relays in the extended H-bonding network of the heme distal side. The latter is required for both catalase and peroxidase reactions. Certain peroxidases have conserved such functional features of the KatG ancestor, although showing a simplified structure of the heme microenvironment as well as differences in the location of Trp (or Tyr) radical sites. Also, certain mono-functional catalases have also conserved the possibility of using protein-based radical sites as alternative intermediates for a peroxidase-like reaction pathway. Our recent complementary approach using de novo designed proteins with a heme-Trp cofactor (collaboration with V. L. Pecoraro, University of Michigan, Ann Arbor) aimed to better understand the physico-chemical properties that fine-tune the stabilization and reactivity of the Trp or Tyr as oxidation sites, will be discussed.

Bifunctional peroxidases (KatGs): A challenging family of enzymes for understanding putative evolutionary strategies in fine-tuning the oxidation reactions catalyzed by heme-Trp● intermediates and related e- transfer mediated by Trp●/Tyr●

253rd National Meeting (2017)

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