Myoglobin active center

Rovira, C., and Parrinello, M. 2000. First-principles molecular dynamics simulations of models of the myoglobin active center. Int. J. Quantum Chem. 80 1172-80. 

Fig. 3.1 The molecular structure of heme b (also called protoporphyrin IX), the active center of myoglobin, hemoglobin, catalases, and peroxidases, among other heme proteins. 

Fig. 3.2 The structure of myoglobin (deoxy form, PDB entry 1AGN, at 1.15 A resolution [3f]). The heme active center is highlighted (van der Waals spheres), as are the proximal and distal histidines (His93 and His64, respectively, shown as sticks).

Synthetic models of myoglobin and hemoglobin are complex molecules that mimic the stereochemical properties of the protein active center [24] and have oxygen affinities similar to those measured for the protein [25-27]. The first heme model that reversibly binds oxygen (i.e. the picket-fence-oxygen complex Fe(TpivPP)(l,2-Melm)(02), shown in Fig. 3.3) was obtained in the early nine-teen-seventies by Collman and coworkers (TpivPP = tetrapivalami-nophenyl porphyrin 2-meIm = 2-methylimidazole) [18]. Research on synthetic models of the protein has led to a deeper understand-... 

Despite all these studies of proteins and synthetic models, many essential aspects of the function of myoglobin and hemoglobin, e.g. the way the protein controls the binding of ligands (02, CO, and NO), the precise structure of the Fe-ligand bonds and the structure-spin-energy relationships at the active center, are a topic of debate [2]. 

Peroxidases and catalases contain high-spin Fe(III) and resemble metmyoglobin in properties. The enzymes are reducible to the Fe(II) state in which form they are able to combine (irreversibly) with 02. We see that the same active center found in myoglobin and hemoglobin is present but its chemistry has been modified by the proteins. The affinity for 02 has been altered drastically and a new group of catalytic activities for ferriheme-containing proteins has emerged. 

These superoxo complexes are relevant models for the naturally occurring oxygen carriers hemoglobin and myoglobin, which contain ferroprotoporphyrin IX as an active center in which the sixth axial postion is occupied by the imidazole moiety of histidine.17 They also intervene as primary oxygen adducts in enzymatic cytochrome P-450 oxygenases.18... 

The reconstitution process is a well practiced methodology to examine the structure-function relationship of proteins. The reconstitution method. Fig. 3-1, (exemplified for myoglobin) involves the exclusion of the native active center from the protein, e.g. an ion or a cofactor, to yield the respective apo-protein (or hollow-protein). The implanting (or reconstitution) of a structurally-related cofactor or ion generates the semisynthetic reconstituted protein that might exhibit new tailored functions that are not present in the native protein. The reconstitution process has been extensively practiced upon studying mechanistic aspects of photoinduced ET... 

Fig. 13. Biological active center in hemoglobin and myoglobin. The filled black circles represent the heme skeletal atoms, and the black circles with white dots represent the peripheral groups of the heme. The cross-hatched circles represent the atoms of the proximal and distal histidine and the white circles with black dots a bound CO ligand. [From D. L. Rousseau and J. M. Friedman, in Biological Applications of Raman Spectroscopy (T. G. Spiro, ed,), Vol. 3, p. 133. Wiley, New York, 1988.]...

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