Distal effects

Distal effects arise from noncovalent interactions of the coordinated dioxygen, carbon monoxide, or other ligand with its surroundings. The protein matrix, the pickets, and the caps are functionally equivalent to an anisotropic solvent matrix that contains a variety of solutes. The limits of this simplification are illustrated in the following example. The electronically similar cobalt meso-, deutero-, and protoporphyrin IX complexes bind dioxygen with similar affinities under identical solvent conditions. When they are embedded in globin, larger differences in affinity and changes in cooperativity are observed. 170 These effects are attributed to the slightly different nestling of the porphyrin molecules in the cleft in hemoglobin or, in the generalization introduced, to slightly different solvation effects.
 

Interaction of the coordinated O2 or CO molecule with solvent molecules or with the protein has a profound influence on kinetics and thermodynamics (see Figure 4.24, and Tables 4.2 and 4.5). As discussed earlier, there is accumulation of negative charge on the dioxygen ligand. The possibility then arises for stabilization of coordination through hydrogen bonding or dipolar interactions with solute molecules,175 porphyrin substituents (such as amide groups in the picket-fence porphyrins 176 and some species of strapped porphyrins 161), or with protein residues* (such as histidine). 

 

Destabilization of coordinated ligands and lowered affinity can result if the coordinated ligand is unable, through steric clash, to achieve its optimum stereochemistry or if the closest neighboring groups are electronegative, as are the ether and ester linkages on capped porphyrins. 31 ,180 We will describe in detail in the next subsection (III. C) the fascinating variety of means by which ligand binding is modulated by distal amino-acid residues.