Hydrophobic heme pocket

In hemoglobin and myoglobin the globin protein protects the ferroheme, which is tucked into a hydrophobic crevice of the protein, known as the heme pocket . 

The heme pocket. The helices of hemoglobin (and myoglobin) form a hydrophobic pocket for the heme and provide an environment where the iron atom reversibly binds oxygen. The chemical structure of heme is shown in figure 5.10 and is described in atomic detail in chapters 10 and 14. (Illustration copyright by Irving Geis. Reprinted by permission.)... 

In Mb, heme is located in the heme pocket via multiple noncovalent interactions such as Fe-His coordination, hydrophobic contacts with several nonpolar amino acid residues, and hydrogen bonding between heme propionates and polar amino acids (69). Therefore, the hemin can be easily removed from the heme pocket under acidic conditions to give apomyoglobin (apoMb) (70, 71). Over the past three decades, a variety of artificial iron porphyrins and porphyrinoids have been incorporated into the apoprotein to reconstitute the... 

Hb Hammersmith /342 Phe->Ser hydrophobic group of heme pocket is replaced by a polar one T form favored... 

Figure 6 Distal and proximal heme pockets of sperm whale deoxymyoglobin. O2 enters into the heme pocket and is noncovalently bound at the distal side or hydrophobic Xe4 pocket, and then forms the covalent bond with heme-iron. The iron-bound O2 is stabilized by His64 via hydrogen-bonding interaction...

Val-67 is one of the hydrophobic contacts between the globin chain and the heme group. Its replacement, in HbM Milwaukee, by a polar residue impairs the binding of heme and may allow water to enter the heme pocket. 

In line with this exclusion of ligands, anions such as F", Ck, CN , and Na" do not have access to the heme iron in oxidized cytochrome c. This could arise from steric hindrance around the heme, from a local concentration of positively charged side chains, or an especially hydrophobic environment for the iron, and the authors favor the latter 44 ) In contrast to this closed-heme pocket picture of the oxidized molecule, and to the behavior of reduced eukaryotic c, reduced c does bind carbon monoxide at physiological pH. Either the c molecule opens up slightly upon reduction or the CO molecule can slip into a hydrophobic pocket that charged anions cannot enter. 

Hfine l(Mi 0a fCDij Phe Ser Kammeirsniith Unstable, loses heme lost, and die j ilar gliimmine tends to 0. >en the heme pocket. Replacement of hydrophobic Phe with... 

Figure 1.2. Crystal structure of the active site of chloroperoxidase (CPO) (EC 1.11.1.10) from C. fumago. Protein framework is shown as ribbons. The heme is buried in a hydrophobic binding pocket containing the iron-coordinating cysteinate ligand. Adapted from the X-ray atomic coordinates of CPO. ...

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.)...

Fluorescence emission spectrum of Mb shows a peak located at 629 nm. The fluorescence lifetime is dominated by decay equal to 17.8 ns with fractional contribution equal to 98%. The peak of the first emission band is close to that of the emission occurring when protoporphyrin is dissolved in water. This could indicate that the heme pocket is polar, altliough X-ray diffraction studies (Fraunenfelder et al. 1979) and fluorescence studies using TNS as a probe (Lakowicz and Keating-Nakamoto, 1984) have indicated that heme pocket of myoglobin is hydrophobic. Anyway, this hydrophobic feature of the heme pocket is characteristic to all hemoproteins. Therefore, one may conclude that porphyrin cannot be an indicator of the polarity of the heme pocket. 

The X-ray structure of cytochrome P-450 from Pseudomonas putida grown on camphor has been determined [5]. Heme is attached to the protein through a cystein residue (Cys357, Fig. 2-15). The heme pocket where dioxygen and substrate molecules are bound is entirely composed of the lipophilic residues of the amino acids Leu, Val and Phe. The hydrophobicity of the active site stabilizes the binding of a nonpolar hydrocarbon substrate to the protein as well as the binding of O2 to iron. The active site is only accessible to the substrate and O2 by transient broadening of the protein channels (for the mechanism of oxidation see modem textbooks of biochemistry). 

---