Effect of covalent links on the structure, spectra, and redox properties of myeloperoxidase--a density functional study.
The enzyme myeloperoxidase shows several unusual properties compared to other peroxidases, e.g. a red-shifted absorption spectrum and a peroxidase activity towards chloride. It has been suggested that this is caused by the unusual covalent links between the heme group and the surrounding protein, but whether it is caused by the two ester links to Glu-242 and Asp-94 or the sulfonium ion linkage to Met-243 is unclear. To investigate these suggestions, we have used density functional theory to study the structure, spectra, and reduction potential of 25 models of myeloperoxidase in the reduced (Fe(II)) and oxidized (Fe(III)) states, as well as in the compound I (formally Fe(V)O) and II (Fe(IV)O or Fe(IV)OH) states, using appropriate models of the linkages to the Asp, Glu, and Met residues (including the back-bone connection between Glu-242 and Met-243) in varying combinations. The calculated spectral shifts indicate that both the ester and sulfonium linkages play a role in the spectral shift. On the other hand, the sulfonium linkage seems to be mainly responsible for the high positive reduction potential for the both ferric/ferrous and compound I/II couples of myeloperoxidase.
Devarajan
Ajitha
A
Department of Theoretical Chemistry, Lund University, Chemical Center, P.O. Box 124, SE-221 00 Lund, Sweden.
Gaenko
Alexander V
AV
Ryde
Ulf
U
D000596:Amino Acids; D000818:Animals; D006801:Humans; D008322:Mammals; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry*; D011487:Protein Conformation; D013057:Spectrum Analysis
D000596:Amino Acids; D009195:Peroxidase