Reactivity of the human hemoglobin "dark side"

Paolo Ascenzi, Loris Leboffe, Fabio Polticelli

Research output: Contribution to journalArticlepeer-review


Summary: Ligand binding to the heme distal side is a paradigm of biochemistry. However, X-ray crystallographic studies highlighted the possibility that O2 and NO2 - may bind to the proximal heme side of ferrous human hemoglobin (Hb) α-chains complexed with the α-hemoglobin stabilizing protein and to ferric human hemoglobin β-chains, respectively. Strikingly, the role generally played by the proximal HisF8 residue is played by the distal HisE7 side chain forming the trans axial ligand of the heme-Fe atom. This: i) brings to light that Hb may utilize both heme distal and proximal sides for ligand discrimination, ii) draws attention to the nonequivalence of α- and β-chains, and iii) highlights the possibility that partially unfolded Hb derivatives may display transient ligand-binding properties different from those of the native globin.

Original languageEnglish
Pages (from-to)121-126
Number of pages6
JournalIUBMB Life
Issue number2
Publication statusPublished - Feb 2013


  • α- and β-chain nonequivalence
  • distal heme side
  • human hemoglobin
  • ligand discrimination
  • proximal heme side
  • transient ligand-binding properties

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics


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