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Structural stability and heme binding potential of the truncated human dual oxidase 2 (DUOX2) peroxidase domain.

http://www.ncbi.nlm.nih.gov/pubmed/21704604

The essential role of human dual oxidase 2 (hDUOX2) in thyroid hormone biosynthesis defines this member of the NOX/DUOX family, whose absence due to mutation has been directly related to disease, specifically hypothyroidism. Both human DUOX isoforms, hDUOX1 and hDUOX2, are expressed in thyroid tissue; however, hDUOX1 cannot compensate for inactivation of hDUOX2, suggesting that each enzyme is differentially regulated and/or functions in a unique manner. In efforts to uncover relevant structural and functional differences we have expressed and purified the peroxidase domain of hDUOX2(1-599) for direct comparison with the previously studied hDUOX1(1-593). As was shown for hDUOX1, the truncated hDUOX2 domain purifies without a bound heme co-factor and displays no peroxidase activity. However, hDUOX2(1-599) displays greater stability than hDUOX1(1-593). Surprisingly, upon titration with heme, both isoforms bind heme with a low micromolar affinity, demonstrating that they retain a heme binding site. A conformational difference in the full-length protein and/or a protein-protein interaction may be required to increase the heme binding affinity.

Pubmed ID: 21704604 RIS Download

Mesh terms: Amino Acid Sequence | Enzyme Stability | Heme | Humans | In Vitro Techniques | Models, Molecular | Molecular Sequence Data | NADPH Oxidase | Peptide Fragments | Protein Conformation | Protein Structure, Secondary | Protein Structure, Tertiary | Recombinant Proteins | Sequence Homology, Amino Acid | Solubility