BPG Binding Site of DeoxyHemoglobin

2,3-BPG Binding Pocket Comparision Between deoxyHb F and deoxyHb A. Hb F Structure Overview

The amino acid residues that form the 2,3-BPG (BPG) binding pockets of deoxyHb F (left) and deoxyHb A (rights) are symmetrically positioned along the surfaces of the γ1/γ2 or β1/β2 subunit interfaces. Whereas deoxyHb A has 8 residues with positively charged ionizable groups, 4 from each β-subunit, deoxyHb F only has 4-6 residues with positively charged ionizable groups, 2-3 from each γ-subunit, Thus, the negatively charged phosphate and carboxyl groups of bound BGP (which is physically absent from either structure here) makes fewer salt briges with deoxyHb F as compared to deoxyHb A.

As summarized in this popup table, these positively charged groups include the side chains of the His 2 and Lys 82 residues of both β or both γ subunits, However, the β-His 143 residues are replaced by γ-Ser 143 residues that lack an ionizable sidechain. Finally, about 15% of the deoxyHb F in circulatiing fetal blood has N-acetylated, γ-Gly1 residues with blocked and nonionizagle α-amino groups, in contast to deoxyHb A where the N-termini of the two β-Val 1 residues are fully ionizable. These groups can be highlighted with the "Spacefill/Zoom' and "Wireframe/Zoom" buttons below and then labeled with the "Charge distribution" and "Charged AA resdiues" checkboxes.

Thus, because fewer positively charged atoms or sidechains line the BPG-binding pocket of dHb F compared to the dHb A pocket, . Thus, fewer salt bridges can form between BPG and the dHb F pocket as compared with dHb A pocket so that BPG binding has less of a stabilizing effect on the dHb F conformation as compared to the dHb A conformation.

The differential binding affinity for BPG by these two isoforms of hemoglobin physiologically fasciliates the O2 transfer from the maternal to the fetal circulatory system because Hb Fwill have a higher average O2 affinity than Hb A at any given BPG concentration so that the oxy/deoxy ratio will tend to be maintained at a higher value for Hb F in fetal blood as compared to Hb A in maternal blood .