The catalytic cycle of catechol oxidase.
Hybrid density functional theory with the B3LYP functional has been used to investigate the catalytic mechanism of catechol oxidase. Catechol oxidase belongs to a class of enzymes that has a copper dimer with histidine ligands at the active site. Another member of this class is tyrosinase, which has been studied by similar methods previously. An important advantage for the present study compared to the one for tyrosinase is that X-ray crystal structures exist for catechol oxidase. The most critical step in the mechanism for catechol oxidase is where the peroxide O-O bond is cleaved. In the suggested mechanism this cleavage occurs in concert with a proton transfer from the substrate. Shortly after the transition state is passed there is another proton transfer from the substrate, which completes the formation of a water molecule. An important feature of the mechanism, like the one for tyrosinase, is that no proton transfers to or from residues outside the metal complex are needed. The calculated energetics is in reasonable agreement with experiments. Comparisons are made to other similar enzymes studied previously.
Siegbahn
Per E M
PE
Department of Physics, Stockholm Centre for Physics, Astronomy and Biotechnology, Stockholm University, 10691 Stockholm, Sweden. ps@physto.se
D001665:Binding Sites; D002384:Catalysis; D004156:Catechol Oxidase / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D006639:Histidine / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011522:Protons; D011789:Quantum Theory; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D008024:Ligands; D011522:Protons; D014867:Water; D006639:Histidine; D003300:Copper; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D010100:Oxygen