Hemoglobin salt bridges

Fig. 2. Reaction of diphosphoglycerate (2,3-DPG) and deoxyhemoglobin. The molecule fits into the central cavity of hemoglobin and forms salt bridges with valine NA(I)p, histidines NA2(2)p, H2I(I43)p, and lysine EF6(82)p. A, E, and E correspond to specific hemoglobin hehces and NA is the sequence...

FIGURE 15.33 Salt bridges between different subunits in hemoglobin. These noncova-... 

Residue H21 of the y subunit of fetal hemoglobin (HbF) is Ser rather than His. Since Ser cannot form a salt bridge, BPG binds more weakly to HbF than to HbA. The lower stabilization afforded to the T state by BPG accounts for HbF having a higher affinity for Oj than HbA. 

Fig. 4. C-terminal salt bridges and the role of the residue F9j8 in the T and R structures of mammalian and fish hemoglobins, (a) Human T structure (b) human R structure (c) carp T structure (d) carp R structure. The letters F, G, and H denote helical segments FG, GH, and HC denote nonhelical segments. The same notation is used in Fig. 5 (23).

The quaternary structure of hemoglobin features strong interactions between unlike subunits. The i/3i interface (and its a2 2 counterpart) involves more than 30 residues, and its interaction is sufficiently strong that although mild treatment of hemoglobin with urea tends to cause the tetramer to disassemble into a/3 dimers, these dimers remain intact. The a (and a2/3i) interface involves 19 residues (Fig. 5-8). Hydrophobic interactions predominate at the interfaces, but there are also many hydrogen bonds and a few ion pairs (sometimes referred to as salt bridges), whose importance is discussed below. 

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.

VIII. Influence of Salt Bridges on Tertiary and Quaternary Structures of Hemoglobin... 

Fifth, we have prepared cross-linked modified hemoglobins—[a(des-Arg)0]A[a0]cXL, [a(des-Arg-Tyr)0]A[a0]cXL, [a(des-Arg)0(NES)]A [a0]cXL, and [a(des-Arg)0]A[a0(NES)]cXL—and used them to investigate the influence of salt bridges on tertiary and quaternary structures of Hb by H NMR spectroscopy (Miura and Ho, 1984). We have found that several features of the H NMR spectra of asymmetrically modified Hbs cannot be accounted for as a spectral sum of the intact dexoy-Hb C and chemically modified Hb A. The H NMR spectra of deoxy [a(des-Arg)0(NES)]A[a0]cXL and deoxy[a(des-ARG)0]A[a0(NES)]cXL at low pH (pH —6.0) cannot be explained simply as a sum of the spectral features specific for the deoxylike and the oxylike quaternary structures. Thus, our results suggest that there exist intermediate structures in which the tertiary and quaternary structural transitions occur asymmetrically about the diad axis of the Hb molecule during the course of successive removal of the salt bridges (Miura and Ho, 1984). 

The alkaline Bohr effect is synchronous with the oxygenation reaction and the liberation of Bohr protons is exactly proportional to the amount of oxygen taken up. The effect also results from specific changes within the hemoglobin molecule and the latest data indicate that 50% of the effect is due to the salt bridge between the imidazole side chain of His... 

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