Format

Send to:

Choose Destination
See comment in PubMed Commons below
IUBMB Life. 2001 Jun;51(6):351-7.

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

Author information

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510, USA.

Abstract

Structural biology is based on the assumption that structural determinations will explain macromolecular function. To examine the basis of these proposals, the structure/function connections in hemoglobin have been examined. Presently the Monod, Wyman, Changeux (MWC) model of hemoglobin function has great validity. In this model, ligand-binding affinities are linked to quaternary structure, and it has been shown that the model describes the function accurately to a high first approximation. To see how this understanding developed, we review two sets of experimental studies in 1970-71 that supported the applicability of MWC to hemoglobin oxygen binding. One set of data from NMR and ligand binding kinetics supported the quaternary-linked nature of binding required by the MWC model. The other approach, by Perutz, proposed a structural basis for MWC, by suggesting that in one quaternary structure the binding of oxygen broke a salt bridge that caused a lowered quaternary-linked affinity. However, experiments since that time, mostly by X-ray crystallography of deoxygenated hemoglobin, have failed to show salt bridges breaking upon ligation, whereas affinities have remained low. This pattern of results shows that the small energies responsible for ligand-binding affinities and reaction rates have not been identified by discrete structural features. Rather, thermodynamic and kinetic data from a variety of spectroscopic studies have played the central role in establishing the MWC model for hemoglobin.

PMID:
11758802
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for John Wiley & Sons, Inc.
    Loading ...
    Write to the Help Desk