Oxygen heme group binding

Hemoglobins share a common molecular architecture, composed of a polypeptide backbone and an iron porphyrin, as illustrated in Fig. 1. Molecular oxygen binds to the Fe at the center of the planar heme b (Fe protoporphyrin IX). The polypeptide adopts the globin fold constructed primarily from a-helices, customarily labeled with the letters A-H. The heme group binds tightly to a hydrophobic pocket formed primarily from the E- and F-helices. and a bond between the heme Fe and the e-nitrogen of a histidine in the F-helix (His F8) provides the only covalent link between the polypeptide and the heme. 

The heme group binds oxygen when the Fe atom is present as iron(II) (Fig. 10.46). The Fe-02 complex is held together by a a bond between an empty Fe(II) Cg orbital and the full o orbital of O2 and a n bond between filled t orbitals on Fe(II) and the half-full k orbitcds of O2. The bound O2 molecule adopts a bent orientation with respect to the Fe atom, partly because that orientation maximizes interactions between orbitals, but also because it is consistent with the spatial constraints imposed by the arrangement of peptide residues in the pocket of the protein containing the heme group. 

The most conspicuous use of iron in biological systems is in our blood, where the erythrocytes are filled with the oxygen-binding protein hemoglobin. The red color of blood is due to the iron atom bound to the heme group in hemoglobin. Similar heme-bound iron atoms are present in a number of proteins involved in electron-transfer reactions, notably cytochromes. A chemically more sophisticated use of iron is found in an enzyme, ribo nucleotide reductase, that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an important step in the synthesis of the building blocks of DNA. 

FIGURE 15.26 Oxygen and carbon monoxide binding to the heme group of myoglobin. 

Each of the subunits, a and P (as well as the closely related myoglobin molecule), has a prosthetic heme group to which the oxygen molecule binds. There are no covalent bonds between the subunits of Hb. The aggregate is maintained by a combination of weak direct subunit-subunit interactions as well as by indirect interactions mediated by the solvent. 

Each subunit carries a heme group (formula on p. 106), with a central bivalent iron ion. When O2 binds to the heme iron (Oxygenation of Hb) and when O2 is released (Deoxygenation), the oxidation stage of the iron does not change. Oxidation of Fe "" to Fe " only occurs occasionally. The oxidized form, methemoglobin, is then no longer able to bind O2. The proportion of Met-Hb is kept low by reduction (see p. 284) and usually amounts to only 1-2%. 

Cellular oxygen is bound by myoglobin molecules that store it until it is required for metabolic action, where upon they release it to other acceptors. Hemoglobin has a additional function, however, and that is to carry CO2 back to the lungs this is done by certain amino acid side chains, and the heme groups are not directly involved. Because the circumstances under which Hb and Mb are required to bind and release O2 are very different, the two substances have quite different binding constants as a function of O2 partial pressure (Fig.). 

Thus, for hemoglobin (Hb) the oxygen binding curves are sigmoidal as is shown in the above figure. The fact that n exceeds the unit can be ascribed physically to the fact that attachment of O2 to one heme group... 

FIGURE 5-2 The heme group viewed from the side. This view shows the two coordination bonds to Fe2+ perpendicular to the porphyrin ring system. One of these two bonds is occupied by a His residue, sometimes called the proximal His. The other bond is the binding site for oxygen. The remaining four coordination bonds are in the plane of, and bonded to, the flat porphyrin ring system. 

Myoglobin contains a heme prosthetic group, which binds oxygen. Heme consists of a single atom of Fe2+ coordinated within a porphyrin. Oxygen binds to myoglobin reversibly this... 

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