| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5371471 | Biophysical Chemistry | 2010 | 7 Pages |
Ligand binding to the heme distal side is a paradigm of heme-protein biochemistry, the proximal axial ligand being in most cases a His residue. NO binds to the ferrous heme-Fe-atom giving rise to hexa-coordinated adducts (as in myoglobin and hemoglobin) with His and NO as proximal and distal axial ligands, respectively, or to penta-coordinated adducts (as in soluble guanylate cyclase) with NO as the axial distal ligand. Recently, the ferrous derivative of Alcaligenes xylosoxidans cytochrome câ² (Axcyt câ²) and of cardiolipin-bound horse heart cytochrome c (CL-hhcyt c) have been reported to bind NO to the “dark side” of the heme (i.e., as the proximal axial ligand) replacing the endogenous ligand His. Conversely, CL-free hhcyt c behaves as ferrous myoglobin by binding NO to the heme distal side, keeping His as the proximal axial ligand. Moreover, the ferrous derivative of CL-hhcyt c binds CO at the heme distal side, the proximal axial ligand being His. Furthermore, CL-hhcyt c shows peroxidase activity. In contrast, CL-free hhcyt c does not bind CO and does not show peroxidase activity. This suggests that heme-proteins may utilize both sides of the heme for ligand discrimination, which appears to be modulated allosterically. Here, structural and functional aspects of NO binding to ferrous Axcyt câ² and (CL-)hhcyt c are reviewed.
Graphical AbstractDownload full-size imageResearch HighlightsâºCytochromes bind NO at the “dark side” of the heme. âºNO and CO discrimination by Alcaligenes xylosoxidans cytochrome c´. âºCardiolipin is an allosteric modulator of horse heart cytochrome c. âºNO and CO discrimination by cardiolipin-bound horse heart cytochrome c. âºCardiolipin, NO and CO modulate horse heart cytochrome c roles in apoptosis.
