STRUCTURAL BASIS OF LIGAND AFFINITIES OF OXYGEN CARRIERS

The interaction of ligands, such as dioxygen, with metal complexes, such as iron-porphyrinato systems, and the means by which this interaction is characterized, have been covered in broad outline in the previous sections. As noted earlier, the affinities of hemoglobins for carbon monoxide and dioxygen span a wide range (see Table 4.2 and Figure 4.24). In this section the active site is examined in much finer detail than before in order to develop relationships between perturbations in structure and affinity (and hence function)-so called structure-function relationships. The reference point is the somewhat hypothetical situation where the dioxygen binder is in the gas phase and independent of interactions with solvent molecules, solute molecules, and itself, and where dioxygen, carbon monoxide, and other small molecules may bind without steric constraints-in other words, a state where intrinsic affinity is measured. In this section attention is focused exclusively on the hemoglobin family and on ironand cobalt-porphyrinato systems. In recent years structural data on hemoglobin, myoglobin, and their derivatives have become available with a precision that permits meaningful comparison with the more precisely determined model or synthetic systems. In addition, the various hemoglobins and myoglobins, and especially the naturally occurring mutants of hemoglobin A (human Hb), have provided a sort of poor man's site-directed mutagenesis. Now the techniques of molecular biology permit the site of mutation to be selected, the altered gene to be inserted into E. coli, and the mutant protein to be expressed in large (mg) quantities. With the conditions for crystallization of hemoglobins now well-established, we can discover quite rapidly what structural perturbations are caused by the substitution of one amino acid for another, and can relate these to the perturbations in properties, such as cooperativity, dioxygen affinity, and kinetics of ligand binding.
 

The principles enunciated here are applicable generally to hemerythrin and hemocyanin; however, we currently lack the thermodynamic and especially structural data we would like to have for these systems.