MYOGLOBIN AND HEMOGLOBIN 351
crystallographic data comparable to Mb oxyheme stereochemistry (see Table
7.1 ). In fact, the oxygenated picket fence porphyrin model ’ s X - ray structure
was known before that of the oxyhemoproteins and anticipated the correct
bent geometry of the dioxygen molecule. As described above, the bent geom-
etry facilitates metaldπ to O 2 ( π * ) bonding (see Figure 7.3 ). Model compounds
also include substitutions for the proximal histidine ligand. Figure 7.10 shows
substitution by a 1 - or 2 - methylimidazole (1 - MeIm or 2 - MeIm). The proximal
2 - MeIm ligand of the model compounds is sterically more demanding, causing
lengthening of the Fe – O bond, and models the T state (lower dioxygen affi nity),
whereas the proximal 1 - MeIm ligand models the R state (see Figure 7.10 ).
The information of Tables 7.1 and 7.2 indicates that a water molecule is
found in the binding cavity ofα chains of hemoglobin A (HbA) even though
this cavity has been called hydrophobic. Indeed, although many hydrophobic
groups such as valine, leucine, isoleucine, and phenylalanine are positioned
over the porphyrin, the immediate vicinity of the binding site is in fact polar,
containing distal histidine, the heme itself, and associated water molecules.
Model 1 (deoxy) in Table 7.1 should be a good match for deoxy Hb and be
considered as a T - state model compound (see Figures 7.4 , left, and 7.10A ).
Model 2 (oxy) in Table 7.2 should be a good match with HbO 2 and be consid-
ered an R - state model compound (see Figures 7.4 , right, and 7.10B ). The ori-
entation of the proximal, axial base (i.e., the angle φ in Table 7.1 ), the distance
of Fe out of the porphyrin plane for deoxy HbA, as well as Mb, and the model
compound Fe(T piv )PP - (2 - MeIm), model 1, are similar. In Table 7.2 , model 2,
TABLE 7.1 Deoxy - Heme Stereochemistry for Mb, Hb, and Model Compounds
M b^14 HbA ( α H 2 O) a ( β )^15 Fe Model 1 b (Deoxy)^6
Fe – N p , Å c 2.03 (10) 2.08 (3) 2.072 (5)
2.05 (3)
Fe – N Im , Å c 2.22 2.16 (6) 2.095 (6)
2.09 (6)
Fe – Porph, Å 0.42 0.40 (5) 0.43
φ , deg d 19 18 (1) 22.8
Tilt, deg d 11 12 (2) 9.6
a α and β refer to the particular protein chains in myoglobin or hemoglobin. One notes from the
table that the bond distances and angles are slightly different for the two moieties. In each table
cell, data are reported in order α and then β.
b Fe model 1 (deoxy form) Fe(T piv )PP - (2 - MeIm). The porphyrin ligand, Fe(T piv )PP, is the picket
fence porphyrin, meso - tetrakis( α , α , α , α - o - pivalamidephenyl)porphyrin (Figure 16 of reference
9 ). In this chapter see Figure 7.9B.
c F e – N p is the bond distance to porphyrin nitrogen ligand atoms. Fe – N Im is the bond distance to
histidine (or imidazole in model compounds) nitrogen ligand atoms.
d φ is defi ned as the angle between the plane of the axial base (imidazole or histidine) and the
plane defi ned by the metal, the N ligands of the porphyrin ring and the axial base. Tilt is defi ned
as the angle the axial base moves away from the normal to the metal – porphyrin plane and is
affected by methyl substituents such as those on Fe(T piv )PP – (2 - MeIm).