Hemoglobin distal, proximal histidine

Figure 3 Simplified structure of the oxyheme imit in myoglobin and hemoglobin. There are two characteristic histidines in the heme pocket, proximal (F8) and distal (E7) histidines. The latter histidine strongly stabilizes the iron-boimd02 via hydrogen-bonding interaction...

Fe to shift into the ring center. The proximal histidine in the Fe coordination sphere (see Fig, lb) also moves and acts as a means of communicating between sub-units. Another feature of hemoglobin is designed to lessen its affinity for other ligands. The position of the distal histidine shown in Fig. lb forces coordination in a nonlinear geometry. This is favorable for 02 but not for strongly... 

In this section, the question raised above will be addressed by applying the local control methodology to a two-dimensional quantum model of the active site of hemoglobin. This system has been studied extensively for many years, both theoretically and experimentally, using a wide range of theoretical methods or experimental techniques. For a recent review of the theoretical approaches, see Ref. 144 and references therein. Here, we choose the six-coordinated iron-porphyrin-imidazole-CO (FeP(Im)-CO) as active site model, which recently has also been used for the study of the excited states [145]. In this complex, the imidazole mimics the proximal histidine, which binds to the central Fe atom and a second imidazole is placed in the proximity of the complex, to include the influence of the distal histidine. The respective configuration is sketched in Fig. 8. 

Fig. 7.11. Myoglobin and hemoglobin. Myoglobin consists of a single polypeptide chain, which is similar in structure to the a and P subunits of hemoglobin. In all of the subunits, heme is tightly bound in a hydrophobic binding pocket. The proximal histidine extends down from a helix to bind to the Fe atom. The oxygen binds between the distal histidine and the heme. Panel C displays the quaternary structure of hemoglobin (From Frescht A. Structure and Mechanism in Protein Science. New York WH Freeman and Company, 1999. Used with permission.)...

As in myoglobin, hemoglobin (Fig. 7-23), and cytochrome c (see Fig 16-8), one axial coordination position on the iron of most heme proteins (customarily called the proximal position) is occupied by an imidazole group of a histidine side chain. However, in cytochrome P450 and chloroperoxidase a thiolate (-S ) group from a cysteinyl side chain, and in catalase a phenolate anion from a tyrosyl side chain, occupies the proximal position. The sixth or distal coordination position is occupied by the sulfur atom of methionine in cytochrome c and most other cytochromes with low-spin iron but cytochromes b5 and c3 have histidine. The high-spin heme proteins, such as cytochromes c, ... 

Comparison of the primary sequences of hemoglobin chains from more than 60 different species reveals that only nine residues in the polypeptide chain are invariant (i.e. the same) between all of the species. These nine residues include the proximal and distal histidines which are essential for the correct functioning of the protein. Many of the other residues are replaced from one species... 

Model hemes coordinated to phenoxides and aryl thiolates have been investigated as models of catalase and hemoglobins M (which have tyrosine substituted for either the proximal or distal histidine) and cytochromes P450 (which have the thiolate of cysteine coordinated to... 

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