Spectroscopic contributions to the understanding of hemoglobin function: implications for structural biology

Area of Science:

• Structural biology
• Biophysics
• Biochemistry

Background:

• Structural biology often assumes determined structures explain macromolecular function.
• Hemoglobin's structure-function relationship is a key area of study.
• The Monod, Wyman, Changeux (MWC) model provides a framework for hemoglobin function.

Purpose of the Study:

• To examine the structure-function connections in hemoglobin.
• To review experimental studies supporting the Monod, Wyman, Changeux (MWC) model for hemoglobin oxygen binding.
• To assess the role of structural determinations versus thermodynamic/kinetic data in understanding hemoglobin function.

Main Methods:

• Review of experimental studies from 1970-71, including Nuclear Magnetic Resonance (NMR) and ligand binding kinetics.
• Analysis of X-ray crystallography data of deoxygenated hemoglobin.
• Examination of thermodynamic and kinetic data from spectroscopic studies.

Main Results:

• NMR and kinetic data supported the quaternary-linked binding required by the MWC model.
• Perutz's proposed structural basis involving salt bridges breaking upon ligation was not experimentally supported by subsequent X-ray crystallography.
• Experiments failed to identify discrete structural features responsible for the small energies governing ligand-binding affinities and reaction rates.

Conclusions:

• The Monod, Wyman, Changeux (MWC) model accurately describes hemoglobin function.
• Thermodynamic and kinetic data, particularly from spectroscopic studies, have been crucial in establishing the MWC model for hemoglobin.
• Discrete structural features have not explained the energies underlying hemoglobin's ligand-binding affinities and reaction rates.