Cytochromes: Reactivity of the "dark side" of the heme

Paolo Ascenzi (1, 2) , Roberto Santucci (3) , Massimo Coletta (3, 4) , Fabio Polticelli (1)

1 Department of Biology
2 Interdepartmental Laboratory for Electron Microscopy
3 Department of Experimental Medicine and Biochemical Sciences
4 Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems (CIRCMSB)

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 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. Over the last decade, the ferrous derivative of cytochrome (Axcyt ') and of cardiolipin-bound horse heart cytochrome (CL-hhcyt ) have been reported to bind NO to the "dark side" of the heme (, as the proximal axial ligand) replacing the endogenous ligand His. Conversely, CL-free hhcyt 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 binds CO at the heme distal side, the proximal axial ligand being His. Furthermore, CL-hhcyt shows peroxidase activity. In contrast, CL-free hhcyt 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 ' and (CL-)hhcyt are reviewed.

Mots clés: Axcyt; CL; CL-hhcyt; cyt; hhcyt; Mb; Heme-proteins; cytochrome; Horse heart cytochrome; Nitrogen monoxide; Carbon monoxide; Ligand binding; Peroxidase activity; Heme-ligand geometry; Allostery

Domaines: Chimie-Physique [physics.chem-ph]

Paolo Ascenzi, Roberto Santucci, Massimo Coletta, Fabio Polticelli. Cytochromes: Reactivity of the "dark side" of the heme. Biophysical Chemistry, 2010, 152 (1-3), pp.21. ⟨10.1016/j.bpc.2010.09.008⟩. ⟨hal-00694281⟩