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

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

Authors

  • Meitzler JL
  • Ortiz de Montellano PR

Journal

Archives of biochemistry and biophysics

Publication Data

August 15, 2011

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK30297
  • Agency: NCRR NIH HHS, Id: P41 RR001614
  • Agency: NCRR NIH HHS, Id: P41 RR001614-27
  • Agency: NCRR NIH HHS, Id: P41RR001614
  • Agency: NIDDK NIH HHS, Id: R01 DK030297
  • Agency: NIDDK NIH HHS, Id: R01 DK030297-28A1

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