Oxygen binding to catalase-peroxidase

By means of quantum mechanics/molecular mechanics calculations, we show that binding of dioxygen to the FeIII enzyme catalase-peroxidase (KatG), responsible for activating the antitubercular drug isoniazid, is possible in the absence of an external reducing agent, thanks to the unique electronic properties of the active site Met-Tyr-Trp adduct. The calculations give support to recent experimental observations suggesting that KatG activates molecular oxygen and suggest that dioxygen activation may be achieved in other enzymes by inserting a residue with low ionization potential near the active site. © 2011 American Chemical Society.The authors thank the Ministerio de Ciencia e Innovación of Spain (MICINN, Grant FIS2008-03845), Generalitat de Catalunya (Grant 2009SGR-1309), NSERC, and the Canada Research Chair Program.Peer Reviewe