Myoglobin and hemoglobin function by reversibly binding dioxygen at heme sites. Both are globular proteins, that is simply globe-shaped, and over 90% alpha-helical. They are by far the most studied metalloproteins because of their obvious physiological importance and because they could be easily isolated and purified by more traditional chemical methods.Oxygen binders
| Myoglobin's ribbon structure with the cofactor and important active site residues, such as the distal and proximal histidines, are illustrated. Hemoglobin has very similar active site structure, except that it has 4 subunits with 4 different heme groups. This allows cooperative O2 binding , as we'll discuss in class. |  |
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The heme cofactor is easily removed leaving the apoprotein behind. You should know what an apoprotein is. Apomyoglobin retains its helical structure and globular fold even in the abscence of the heme. It is relatively straightforward to reconstitute the apomyoglobin with another cofactor to reform the active myoglobin; in fact, it will reconstitute with metal-substituted hemes, forming unnatural forms such as the Co or Mn substituted myoglobins. |
| The heme site, shown in red, is very close to the surface. This allows rapid binding of dioxygen or other small molecules from solution. |  |
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The heme cofactor is bound to the protein through one axial histidine from the proximal pocket (below the heme as shown). Another important residue is in the distal pocket, above the heme, which is where substrates like dioxygen bind. A distal histidine (a common feature in many different heme proteins) hydrogen-bonds to bound dioxygen, stabilizing the weakly bound form. The pocket is somewhate hydrophilic, water is bound to the FeIII form, again H-bound to the distal His. |
Here is a simple cartoon depicting the reversible binding of dioxygen in the distal pocket of myoglobin:
