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

Paolo Ascenzi, Roberto Santucci, Massimo Coletta, Fabio Polticelli

Research output: Contribution to journalArticlepeer-review


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 c′ (Axcyt c′) 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 c′ and (CL-)hhcyt c are reviewed.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalBiophysical Chemistry
Issue number1-3
Publication statusPublished - Nov 2010


  • Alcaligenes xylosoxidans cytochrome c'
  • Allostery
  • Carbon monoxide
  • Heme-ligand geometry
  • Horse heart cytochrome c
  • Nitrogen monoxide

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Organic Chemistry


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