Hemoglobin structural changes

BR Gelm, M Karplus. Mechanism of tertiary structural change m hemoglobin. Proc Natl Acad Sci USA 74 801-805, 1977. 

Gelin BR, Lee AW-M, Karpls M. 1983. Hemoglobin tertiary structural change on ligand binding. J Mol Biol 171 ... 

Hemoglobin Undergoes a Structural Change on Binding Oxygen... 

Sigmoid kinetic behavior generally reflects cooperative interactions between protein subunits. In other words, changes in the structure of one subunit are translated into structural changes in adjacent subunits, an effect mediated by noncovalent interactions at the interface between subunits. The principles are particularly well illustrated by a nonenzyme 02 binding to hemoglobin. Sigmoid kinetic behavior is explained by the concerted and sequential models for subunit interactions (see Fig. 5-15). 

Schematic diagram showing structural changes resulting from oxygenation and deoxygenation of hemoglobin.

Figure 7-25 (A) Structural changes occurring upon oxygenation of hemoglobin. After Dickerson144 and Perutz.143 (B) "Rotation at the contact ot, p2 causes a jump in the dovetailing of the CD region of a relative to the FG region of 3 and a switch of hydrogen bonds as shown".143 (C) Some details of the salt bridges.

The bell-shaped curve is of particular interest in the analysis of how structural changes in a protein affect L. The Hill constants of a wide series of modified and mutant hemoglobins fit such a curve (Figure 10.9).19... 

The choice of model often depends on the experiments involved. Workers in the area of, say, the effects of structural changes on the oxygen affinity and Hill constant for hemoglobin prefer the MWC model because it is essentially a structural theory. It provides a simple framework for the prediction and interpretation of experiments. Application of the theory to the Hill constant and other equilibrium measurements gives very acceptable results. Kineticists prefer the KNF model, since the kinetic measurements are more sensitive to the presence of intermediates. There are more variables in the KNF theory and there is more flexibility in fitting data. 

V. H NMR Investigations of Partially Oxygenated Species of Hemoglobin Evidence for Nonconcerted Structural Changes during the Oxygenation Process... 

Hemoglobin dramatically demonstrates how sensitive the function of a biomolecule is to its structure. In certain people, in the synthesis of the proteins needed for hemoglobin, an improper amino acid is inserted into the protein in two places. This may not seem very serious, since there are several hundred amino acids present. However, because the incorrectly inserted amino acid has a nonpolar substituent instead of the polar one found on the proper amino acid, the hemoglobin drastically changes its shape. The red blood cells are then sickle-shaped rather than disk-shaped, as shown in Fig. 20.37. The misshapen cells can aggregate, causing clogging of tiny capillaries. This condition, known as sickle cell anemia, is the subject of intense research. 

Goldbeck RA, Esquerra RM, Holt JM, Ackers GK, Kliger DS. The molecular code for hemoglobin allostery revealed by linking the thermodynamics and kinetics of quaternary structural change. 1. Microstate linear free energy relations. Biochemistry 2004 43 12048-12064. 

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