Gly pathological mutant hemoglobins such as

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Gly), pathological mutant hemoglobins, such as hemoglobin Zurich (j3E7His -? Arg), and some others, such as elephant hemoglobin. Long be- lieved to be noncoordinating, this distal histidine may, in fact, coordinate weakly to the Fe center at low temperature. 159 In the a chains of human deoxyhemoglo- Table 4.7 Metrical details of deoxyhemoglobins and their models a Resol. Fe;N p Fe ... Porp DOl!Jing Fe-N hn </> Tilt Compound (;\) (A) (;\) (A) (;\) (deg) (deg) Fe(PF)(2-Melm) 2.072(5) 0.43 0.03 2.095(6) 22.8 9.6 Fe(TPP)(2-Melm) 2.086(6) 0.40 0.13 2.161(5) 7.4 10.3 Mb 1.4 2.03(10) 0.42 0.08 2.22 19 11 Er' .. H 2 O 1.4 2.02 0.17 -0.06 2.25 7 3 HbA (a' .. H 2 O) 1.74 2.08(3) 0.40(5) 0.16(6) 2.16(6) 18(1) 12(2) (f3) 2.05(3) 0.36(5) 0.10(6) 2.09(6) 24(1) 11(2) CoHbb 2.5 0.14(5) 0.13 2.24(6) Co(TPP)( I-Melm) 1.977(6) 0.13 0.01 2.157(3) 3.8 0 Co(TPP)(I, 2-Me2Im) 1.985(3) 0.15 0.05 2.216(2) 10 a See Figure 4.25 for definition of symbols. b From a difference refinement of CoHb vs. Hb, where the difference in metal-to-porphyrin-plane separation was 0.24(2);\ and the difference in M-N 1m was 0.13(4) A. Doming is similar to Hb.
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232 4 / BIOLOGICAL AND SYNTHETIC DIOXYGEN CARRIERS bin, hemoglobin A, a water molecule is found in the binding cavity. 182 For many years the binding cavity has been referred to as the hydrophobic pocket- literally, water-hating. Although many hydrophobic groups, such as valine, leu- cine, isoleucine, and phenylalanine are positioned over the porphyrin, the im- mediate environment around the binding site is, in fact, polar, with the distal histidine and associated water molecules, as well as the heme group itself. As will be shown in the next section, the label "hydrophobic pocket" becomes more misleading when the interaction of coordinated ligands with distal groups is examined. The orientation of the axial base, angle 1>1, is similar for Fe(PF)(2-MeIm) and for several vertebrate deoxyhemoglobins. On the other hand, Fe(TPP)(2- Melm) and deoxyerythrocruorin have a similar eclipsed axial-base orientation. At least for five-coordinate species, where the iron center is substantially out of the porphyrin plane, orientation of the axial base does not invariably induce structural perturbations, e.g., doming, in the porphyrin skeleton. The conformation of the protein chain is such that the proximal histidine in deoxyhemoglobin coordinates in a slightly tilted manner,182,186 comparable to the tilt that the sterically active 2-methyl substituent induces in the synthetic systems. 172 Clearly, coordination of the histidine to the heme in a symmetric manner, as would be expected in the absence of the protein constraints, does not produce the conformation of lowest free energy for the whole molecule. 2. Structures relevant to liganded hemoglobins a. Stereochemistry of the Active Site Before the advent of techniques that enabled the preparation and stabilization of oxyhemoglobin crystals, key infor- mation on the probable structure of oxyhemoglobin and thence on the mecha- nism of cooperativity was extrapolated from structures of methemoglobin derivatives II and from various five- and six-coordinate cobalt-porphyrinato complexes.
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