Conformational dependence of hemoglobin reactivity under high viscosity conditions

The role of solvent slaved dynamics

Uri Samuni, Camille J. Roche, David Dantsker, Joel M. Friedman

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The concept of protein dynamic states is introduced. This concept is based on (i) protein dynamics being organized hierarchically with respect to solvent slaving and (ii) which tier of dynamics is operative over the time window of a given measurement. The protein dynamic state concept is used to analyze the kinetic phases derived from the recombination of carbon monoxide to sol-gel-encapsulated human adult hemoglobin (HbA) and select recombinant mutants. The temperature-dependent measurements are made under very high viscosity conditions obtained by bathing the samples in an excess of glycerol. The results are consistent with a given tier of solvent slaved dynamics becoming operative at a time delay (with respect to the onset of the measurement) that is primarily solvent- and temperature-dependent. However, the functional consequences of the dynamics are protein- and conformation-specific. The kinetic traces from both equilibrium populations and trapped allosteric intermediates show a consistent progression that exposes the role of both conformation and hydration in the control of reactivity. Iron-zinc symmetric hybrid forms of HbA are used to show the dramatic difference between the kinetic patterns for T state α and β subunits. The overall results support a model for allostery in HbA in which the ligand-binding-induced transition from the deoxy T state to the high -affinity R state proceeds through a progression of T state intermediates.

Original languageEnglish (US)
Pages (from-to)12756-12764
Number of pages9
JournalJournal of the American Chemical Society
Volume129
Issue number42
DOIs
StatePublished - Oct 24 2007

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Hemoglobin
Viscosity
Hemoglobins
Proteins
Protein Conformation
Temperature
Polymethyl Methacrylate
Carbon Monoxide
Operative Time
Glycerol
Genetic Recombination
Kinetics
Conformations
Zinc
Iron
Gels
Ligands
Carbon monoxide
Hydration
Population

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Conformational dependence of hemoglobin reactivity under high viscosity conditions : The role of solvent slaved dynamics. / Samuni, Uri; Roche, Camille J.; Dantsker, David; Friedman, Joel M.

In: Journal of the American Chemical Society, Vol. 129, No. 42, 24.10.2007, p. 12756-12764.

Research output: Contribution to journalArticle

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