1. Active site structure and catalytic mechanisms of human peroxidases
- Author
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Christa Jakopitsch, Christian Obinger, Paul G. Furtmüller, Jutta Helm, Walter Jantschko, Martin Bogner, and Martina Zederbauer
- Subjects
Protein Conformation ,Stereochemistry ,Molecular Sequence Data ,Biophysics ,Biochemistry ,Catalysis ,Substrate Specificity ,Structure-Activity Relationship ,chemistry.chemical_compound ,Humans ,Amino Acid Sequence ,Binding site ,Molecular Biology ,Heme ,chemistry.chemical_classification ,Binding Sites ,biology ,Lactoperoxidase ,Active site ,Enzyme Activation ,Enzyme ,Peroxidases ,chemistry ,Myeloperoxidase ,biology.protein ,Eosinophil peroxidase ,Peroxidase - Abstract
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.
- Published
- 2006