Structural stability and heme binding potential of the truncated human dual oxidase 2 (DUOX2) peroxidase domain |
| |
Authors: | Meitzler Jennifer L Ortiz de Montellano Paul R |
| |
Institution: | Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158-2517, United States |
| |
Abstract: | 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 hDUOX21–599 for direct comparison with the previously studied hDUOX11–593. As was shown for hDUOX1, the truncated hDUOX2 domain purifies without a bound heme co-factor and displays no peroxidase activity. However, hDUOX21–599 displays greater stability than hDUOX11–593. 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. |
| |
Keywords: | DUOX2 DUOX1 Peroxidase stability Heme binding Heme titration |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|