Density functional methods applied to metalloenzymes

Density functional calculations for structures, spin states, redox energetics and reaction pathways are presented for some selected metalloenzymes. The specific enzymes examined are: (1) Fe and Mn superoxide dismutase for redox energetics and the role of second shell residues; (2) galactose oxidase (Cu enzyme) and (3) glyoxalase I (Zn enzyme) for reaction pathways, mechanisms, intermediates, and transition states (reaction barriers); (4) iron-oxo dimer enzymes methane monooxygenase and ribonucleotide reductase for characterizing the oxidized and reduced forms in terms of structures and protonation states, and for a proposed structure for the high-valent intermediate Q in MMO. The interaction of the active site with the surrounding protein environment is also explored in a number of cases either by using expanded quantum mechanically treated clusters, or by using electrostatic/ dielectric representations of the protein-solvent environment. (C) 2003 Elsevier Science B.V. All rights reserved.