Active site structure and catalytic mechanisms of human peroxidases.
Myeloperoxidase (MPO), eosinophil peroxidase, lactoperoxidase, and thyroid peroxidase are heme-containing oxidoreductases (EC 1.7.1.11), which bind ligands and/or undergo a series of redox reactions. Though sharing functional and structural homology, reflecting their phylogenetic origin, differences are observed regarding their spectral features, substrate specificities, redox properties, and kinetics of interconversion of the relevant redox intermediates ferric and ferrous peroxidase, compound I, compound II, and compound III. Depending on substrate availability, these heme enzymes path through the halogenation cycle and/or the peroxidase cycle and/or act as poor (pseudo-)catalases. Based on the published crystal structures of free MPO and its complexes with cyanide, bromide and thiocyanate as well as on sequence analysis and modeling, we critically discuss structure-function relationships. This analysis highlights similarities and distinguishing features within the mammalian peroxidases and intents to provide the molecular and enzymatic basis to understand the prominent role of these heme enzymes in host defense against infection, hormone biosynthesis, and pathogenesis.
Furtmüller
Paul G
PG
Department of Chemistry, Division of Biochemistry, Metalloprotein Research Group, Muthgasse 18, A-1190 Vienna, Austria.
Zederbauer
Martina
M
Jantschko
Walter
W
Helm
Jutta
J
Bogner
Martin
M
Jakopitsch
Christa
C
Obinger
Christian
C
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D004789:Enzyme Activation; D006801:Humans; D008969:Molecular Sequence Data; D010544:Peroxidases / Q000737:chemistry* / Q000502:physiology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D010544:Peroxidases