Catalase evolved to concentrate H 2O 2 at its active site

Abstract

Catalase is a homo-tetrameric enzyme that has its heme active site deeply buried inside the protein. Its only substrate, hydrogen peroxide (H 2O 2), reaches the heme through a 45 Å-long channel. Large-subunit catalases, but not small-subunit catalases, have a loop (gate loop) that interrupts the major channel. Two accesses lead to a gate that opens the final section of the channel to the heme; gates from the R-related subunits are interconnected. Using molecular dynamic simulations of the Neurospora crassa catalase-1 tetramer in a box of water (48,600 molecules) or 6 M H 2O 2, it is shown that the number of H 2O 2 molecules augments at the surface of the protein and in the accesses to the gate and the final section of the channel. Increase in H 2O 2 is due to the prevalence and distribution of amino acids that have an increased residency for H 2O 2 (mainly histidine, proline and charged residues), which are localized at the protein surface and the accesses to the gate. In the section of the channel from the heme to the gate, turnover rate of water molecules was faster than for H 2O 2 and increased residence sites for water and H 2O 2 were determined. In the presence of H 2O 2, the exclusion of water molecules from a specific site suggests a mechanism that could contend with the competing activity of water, allowing for catalase high kinetic efficiency.