Few structural data are available for high-affinity oxygen carriers. The crystal structures of two leghemoglobin derivatives, a monomeric myoglobin-like oxygen carrier found in the nitrogen-fixing nodules of legumes, are known at 2.0 and 3.3 A.Z04,Z05 The binding pocket appears more open, perhaps allowing HzO to enter and partake in stronger hydrogen bonding than that offered by the distal imidazole. Consistent with this notion is the more rapid rate of autoxidation observed for oxyleghemoglobin. Aplysia oxymyoglobin, which lacks a distal histidine, also autoxidizes rapidly,2°4 although a distal arginine further along the helix E, ElOArg, fulfills the role of the distal histidine by hydrogen bonding to the sixth ligand, at least in the fluoride derivative, met-MbF.
Although no structural data are available, a tenfold increase in Oz affinity was observed between an ester-strapped porphyrin, offering no hydrogen-bonding possibilities, and its confonnationally very similar amide analogue. Oz, .. amide hydrogen bonding was demonstrated by means of NMR shift data (Zn and Fe-CO complexes vs. the Fe-02 complex) and from infrared spectroscopy, which showed shifted amide N-H absorptions.
The specific structural features that lead to the extraordinarily high affinity for O2 and low affinity for CO in hemoglobin Ascaris remain unidentified. This high affinity is due to an extremely slow dissociation rate of O2 of only 0.Is - 1; in most hemoglobins the rate is about 10 to 2,500 s ~ 1 (Table 4.2). Dioxygen binding is thus close to irreversible. Figure 4.27 shows that hydrogen bonding to the coordinated dioxygen ligand, unrestrained motion of the Fe-proximal histidine group into the plane of the porphyrin, hydrogen bonding to the proximal histidine, and, in the deoxy form, compression of the Fe-Nrm bond and decrease in the out-of-plane displacement of the Fe atom will all increase O2 affinity over that of a system where these effects are absent.
When hydrogen bonding is impossible, as in various synthetic systems (Table 4.5) as well as hemoglobin Glycera and Mb(E7His~Gly), O2 affinity is much lower than when hydrogen bonding can occur (see Table 4.6), especially for the cobalt analogues. But caution is needed in the absence of complete structural information: the lowered affinity of Aplysia hemoglobin had been attributed to the lack of a distal histidine and its attendant hydrogen-bonding capabilities. However, the crystal structure reveals that an arginine residue, normally directed out into the solution, is capable of folding back into the ligand-binding pocket and of hydrogen bonding to ligands at the sixth site. In oxyhemerythrin the hydrogen bonding of the coordinated hydroperoxy group to the oxo bridge linking the two iron atoms (Figure 4.lOB), described in Section II.F.I, may not only increase the stability of oxyhemerythrin,146 but also facilitate electron transfer that occurs in dioxygen binding.
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