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09:43
Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
Reactivity of the human hemoglobin "dark side"
Paolo Ascenzi1, Loris Leboffe, Fabio Polticelli
1Laboratorio Interdipartimentale di Microscopia Elettronica, Università Roma Tre, Roma, Italy. ascenzi@uniroma3.it
IUBMB Life
|January 5, 2013
Summary
Human hemoglobin (Hb) can bind ligands on both its distal and proximal sides, challenging biochemical paradigms. This unique binding capability, observed in specific Hb derivatives, suggests a novel mechanism for ligand discrimination.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Chemistry
Background:
- Ligand binding to the distal side of heme is a well-established biochemical principle.
- Previous studies have not extensively explored alternative ligand binding sites within hemoglobin.
Purpose of the Study:
- To investigate the potential for ligand binding on the proximal heme side of human hemoglobin (Hb).
- To explore the role of specific Hb chain types (α and β) and their derivatives in ligand binding.
- To elucidate the structural basis for altered ligand-binding properties in Hb.
Main Methods:
- X-ray crystallographic studies were employed to analyze the structural basis of ligand binding.
- Specific human hemoglobin derivatives, including ferrous Hb α-chains with stabilizing protein and ferric Hb β-chains, were examined.
Main Results:
- O(2) and NO(2)(-) were observed to bind to the proximal heme side of specific Hb derivatives, contrary to established models.
- The distal HisE7 side chain was found to act as the trans axial ligand, mimicking the role of the proximal HisF8 residue.
- Significant nonequivalence in ligand binding was observed between Hb α- and β-chains.
Conclusions:
- Human hemoglobin exhibits a previously unrecognized ability to utilize both distal and proximal heme sides for ligand discrimination.
- The distinct behavior of α- and β-chains highlights their functional nonequivalence in ligand interactions.
- Partially unfolded Hb derivatives may possess transient ligand-binding properties distinct from native Hb, suggesting potential roles in disease states.
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