Coupling of the oxygen-linked interaction energy for inositol hexakisphosphate and bezafibrate binding to human HbA0

Massimo Coletta, Mauro Angeletti, Paolo Ascenzi, Alberto Bertollini, Stefano Della Longa, Giampiero De Sanctis, Anna Maria Priori, Roberto Santucci, Gino Amiconi

Research output: Contribution to journalArticlepeer-review

Abstract

The energetics of signal propagation between different functional domains (i.e. the binding sites for O2, inositol hexakisphospate (IHP), and bezafibrate (BZF)) of human HbA0 was analyzed at different heme ligation states and through the use of a stable, partially heme ligated intermediate. Present data allow three main conclusions to be drawn, and namely: (i) IHP and BZF enhance each others binding as the oxygenation proceeds, the coupling free energy going from close to zero in the deoxy state to -3.4 kJ/mol in the oxygenated form; (ii) the simultaneous presence of IHP and BZF stabilizes the hemoglobin T quaternary structure at very low O2 pressures, but as oxygenation proceeds it does not impair the transition toward the R structure, which indeed occurs also under these conditions; (iii) under room air pressure (i.e. pO2 = 150 torr), IHP and BZF together induce the formation of an asymmetric dioxygenated hemoglobin tetramer, whose features appear reminiscent of those suggested for transition state species (i.e. T- and R-like tertiary conformation(s) within a quaternary R-like structure).

Original languageEnglish
Pages (from-to)6865-6874
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number11
DOIs
Publication statusPublished - Mar 12 1999

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Coupling of the oxygen-linked interaction energy for inositol hexakisphosphate and bezafibrate binding to human HbA0'. Together they form a unique fingerprint.

Cite this