Histidine distal

Figure Bl.2.11. Biologically active centre in myoglobin or one of the subunits of haemoglobin. The bound CO molecule as well as the proximal and distal histidines are shown m addition to the protohaeme unit. From Rousseau D L and Friedman J M 1988 Biological Applications of Raman Spectroscopy vol 3, ed T G Spiro (New York Wiley). Reprinted by pennission of John Wiley and Sons Inc.

DET calculations on the hyperfine coupling constants of ethyl imidazole as a model for histidine support experimental results that the preferred histidine radical is formed by OH addition at the C5 position [00JPC(A)9144]. The reaction mechanism of compound I formation in heme peroxidases has been investigated at the B3-LYP level [99JA10178]. The reaction starts with a proton transfer from the peroxide to the distal histidine and a subsequent proton back donation from the histidine to the second oxygen of the peroxide (Scheme 8). 

Neutron diffraction involves bombarding a solid sample with neutrons to reveal proton and deuteron locations unavailable from X-ray crystallographic analyses. One can place H and D atoms within a structure—for instance, to identify hydrogen bonding of distal histidines to bound O2 in Mb and Hb.23... 

Figure 4.12 Distal histidine hydrogen bonding structure for hemoglobin (left) and a heme model (right). (Reprinted with permission from Figure 12 of Momenteau, M. Reed, C. A. Chem. Rev., 1994, 94, 659-698. Copyright 1994, American Chemical Society.)...

Fig. 3.2 The structure of myoglobin (deoxy form, PDB entry 1AGN, at 1.15 A resolution [3f]). The heme active center is highlighted (van der Waals spheres), as are the proximal and distal histidines (His93 and His64, respectively, shown as sticks).

The A0 component is observed on reducing the pH or mutating the distal histidine residue (His64) [9a, 12]. In addition, an X-ray study of MbCO at low pH [3b] has demonstrated that His64 is far from the ligand and out of the heme pocket. On this basis the A0 state is usually associated with a protein substate in which the CO is in an apolar environment. 

Classical simulations of MbCO using the CHARMM force field were performed for different tautomerization states of the distal histidine residue (His64) [33], These simulations showed that when His64 is protonated at N,5 (denoted the tautomer) it often rotates such that it exposes either the N,>—H bond or the un-protonated N atom to the CO, as depicted in Scheme 3.4. We... 

The haem is tightly bound to the protein in a hydrophobic pocket formed principally by helices E and F and by a single coordinate bond between the imidazole of His F8, termed the proximal histidine (Figure 13.6), and the ferrous iron, which is some 0.6 A out of the plane of the domed porphyrin ring. A second His residue, His E7 (the distal histidine), is too far away from the iron atom to coordinate with it in the deoxy state. 

The nature of reduced form in this variant (His/His or His/- ) is not known with certainty. However, CO is known to displace the distal histidine ligand in ferrous V68H, and it is, therefore, likely that the reduced form in these experiments is deoxy Mb (His/-). 

---