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| Content Provider | PubMed Central |
|---|---|
| Author | Sabat, Joseph Stuehr, Dennis J. Yeh, Syun-ru Rousseau, Denis L. |
| Abstract | The nitric oxide (NO) produced by inducible Nitric Oxide Synthase (iNOS) up-regulates the expression of heme oxygenase (HO), which in turn produces carbon monoxide (CO) that down-regulates iNOS activity by reducing its expression level or by inhibiting its activity by converting it to an inactive P420 form (iNOSP420). Accordingly, CO has been considered as a potentially important attenuator of inflammation. Despite its importance, the nature of the proximal heme ligand of the iNOSP420 species remains elusive. Here we show that the 221 cm−1 mode of the photoproduct of iNOSP420 does not exhibit any H2O-D2O solvent isotope shift such as that found in the iron-histidine stretching mode of myoglobin, indicating that the proximal ligand of iNOSP420 is not a histidine. The νFe-CO and νC-O data reveal that the proximal heme ligand of iNOSP420 is consistent with a protonated thiol, instead of a thiolate anion. Furthermore, the optical absorption properties of iNOSP420 are similar to those of a neutral thiol-heme model complex, but not myoglobin. Together the data support the scenario that iNOSP420 is inactivated by protonation of the native proximal thiolate ligand to a neutral thiol, instead of by ligand switching to a histidine, as prior studies have suggested. |
| Related Links | http://dx.doi.org/10.1021/ja901016a |
| Ending Page | 12192 |
| Page Count | 7 |
| Starting Page | 12186 |
| File Format | |
| ISSN | 00027863 |
| e-ISSN | 15205126 |
| Journal | Journal of the American Chemical Society |
| Issue Number | 34 |
| Volume Number | 131 |
| Language | English |
| Publisher Date | 2009-09-02 |
| Access Restriction | Open |
| Subject Keyword | Colloid and Surface Chemistry Biochemistry Chemistry(all) Catalysis Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Chemistry Colloid and Surface Chemistry Biochemistry Catalysis |
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